Chapter 11

Содержание

1. Chapter 11
2. Overview: The Cellular InternetCell-to-cell communication is essential
3. Fig. 11-1
4. Concept 11.1: External signals are converted to
5. Evolution of Cell SignalingA signal transduction pathway
6. Fig. 11-2Receptor factora factoraaExchangeof matingfactorsYeast cell,mating type aYeast cell,mating type MatingNew a/cella/123
7. Pathway similarities suggest that ancestral signaling molecules
8. Fig. 11-3Individual rod-shaped cellsSpore-formingstructure(fruiting body)Aggregation inprocessFruiting bodies0.5 mm132
9. Local and Long-Distance SignalingCells in a multicellular
10. Fig. 11-4Plasma membranesGap junctionsbetween animal cells(a) Cell junctionsPlasmodesmatabetween plant cells(b) Cell-cell recognition
11. In many other cases, animal cells communicate
12. Fig. 11-5Local signalingTarget cellSecretingcellSecretoryvesicleLocal regulatordiffuses throughextracellular fluid(a)
13. Fig. 11-5abLocal signalingTarget cellSecretoryvesicleSecretingcellLocal regulatordiffuses throughextracellular fluid(a)
14. Fig. 11-5cLong-distance signalingEndocrine cellBloodvesselHormone travelsin bloodstreamto target cellsTargetcell(c) Hormonal signaling
15. The Three Stages of Cell Signaling: A
16. Fig. 11-6-1Reception1EXTRACELLULARFLUIDSignalingmoleculePlasma membraneCYTOPLASM1Receptor
17. Fig. 11-6-21EXTRACELLULARFLUIDSignalingmoleculePlasma membraneCYTOPLASMTransduction2Relay molecules in a signal transduction pathwayReception1Receptor
18. Fig. 11-6-3EXTRACELLULARFLUIDPlasma membraneCYTOPLASMReceptorSignalingmoleculeRelay molecules in a signal transduction pathwayActivationof cellularresponseTransductionResponse23Reception1
19. Concept 11.2: Reception: A signal molecule binds
20. Receptors in the Plasma MembraneMost water-soluble signal
21. A G protein-coupled receptor is a plasma
22. Fig. 11-7aSignaling-molecule binding siteSegment thatinteracts withG proteinsG protein-coupled receptor
23. Fig. 11-7bG protein-coupledreceptorPlasmamembraneEnzymeG protein(inactive)GDPCYTOPLASMActivatedenzymeGTPCellular responseGDPPiActivatedreceptorGDPGTPSignaling moleculeInactiveenzyme1234
24. Receptor tyrosine kinases are membrane receptors that
25. Fig. 11-7cSignalingmolecule (ligand)Ligand-binding site HelixTyrosinesTyrTyrTyrTyrTyrTyrReceptor tyrosinekinase proteinsCYTOPLASMSignalingmoleculeTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrDimerActivated
26. A ligand-gated ion channel receptor acts as
27. Fig. 11-7dSignalingmolecule(ligand)GateclosedIonsLigand-gatedion channel receptorPlasmamembraneGate openCellularresponseGate closed321
28. Intracellular ReceptorsSome receptor proteins are intracellular, found
29. Fig. 11-8-1Hormone(testosterone)ReceptorproteinPlasmamembraneEXTRACELLULARFLUIDDNANUCLEUSCYTOPLASM
30. Fig. 11-8-2ReceptorproteinHormone(testosterone)EXTRACELLULARFLUIDPlasmamembraneHormone-receptorcomplexDNANUCLEUSCYTOPLASM
31. Fig. 11-8-3Hormone(testosterone)EXTRACELLULARFLUIDReceptorproteinPlasmamembraneHormone-receptorcomplexDNANUCLEUSCYTOPLASM
32. Fig. 11-8-4Hormone(testosterone)EXTRACELLULARFLUIDPlasmamembraneReceptorproteinHormone-receptorcomplexDNAmRNANUCLEUSCYTOPLASM
33. Fig. 11-8-5Hormone(testosterone)EXTRACELLULARFLUIDReceptorproteinPlasmamembraneHormone-receptorcomplexDNAmRNANUCLEUSNew proteinCYTOPLASM
34. Concept 11.3: Transduction: Cascades of molecular interactions
35. Signal Transduction PathwaysThe molecules that relay a
36. Protein Phosphorylation and DephosphorylationIn many pathways, the
37. Protein phosphatases remove the phosphates from proteins,
38. Fig. 11-9Signaling moleculeReceptorActivated relaymoleculeInactiveprotein kinase1Activeproteinkinase1Inactiveprotein kinase2ATPADPActiveproteinkinase2PPPPInactiveprotein kinase3ATPADPActiveproteinkinase3PPPPiATPADPPActiveproteinPPPiInactiveproteinCellularresponsePhosphorylation cascadei
39. Small Molecules and Ions as Second MessengersThe
40. Cyclic AMPCyclic AMP (cAMP) is one of
41. Adenylyl cyclaseFig. 11-10PyrophosphatePPiATPcAMPPhosphodiesteraseAMP
42. Many signal molecules trigger formation of cAMPOther
43. First messengerFig. 11-11G proteinAdenylylcyclaseGTPATPcAMPSecondmessengerProteinkinase AG protein-coupledreceptorCellular responses
44. Calcium Ions and Inositol Triphosphate (IP3)Calcium ions
45. EXTRACELLULARFLUIDFig. 11-12ATPNucleusMitochondrionCa2+ pumpPlasmamembraneCYTOSOLCa2+pumpEndoplasmicreticulum (ER)Ca2+pumpATPKeyHigh [Ca2+]Low [Ca2+]
46. A signal relayed by a signal transduction
47. Fig. 11-13-1EXTRA-CELLULARFLUIDSignaling molecule(first messenger)G proteinGTPG protein-coupledreceptorPhospholipase CPIP2IP3DAG(second messenger)IP3-gatedcalcium channelEndoplasmicreticulum (ER)Ca2+CYTOSOL
48. Fig. 11-13-2G proteinEXTRA-CELLULARFLUIDSignaling molecule(first messenger)G protein-coupledreceptorPhospholipase CPIP2DAGIP3(second messenger)IP3-gatedcalcium channelEndoplasmicreticulum (ER)Ca2+CYTOSOLCa2+(secondmessenger)GTP
49. Fig. 11-13-3G proteinEXTRA-CELLULARFLUIDSignaling molecule(first messenger)G protein-coupledreceptorPhospholipase CPIP2DAGIP3(second messenger)IP3-gatedcalcium channelEndoplasmicreticulum (ER)Ca2+CYTOSOLVariousproteinsactivatedCellularresponsesCa2+(secondmessenger)GTP
50. Concept 11.4: Response: Cell signaling leads to
51. Nuclear and Cytoplasmic ResponsesUltimately, a signal transduction
52. Fig. 11-14Growth factorReceptorPhosphorylationcascadeReceptionTransductionActivetranscriptionfactorResponsePInactivetranscriptionfactorCYTOPLASMDNANUCLEUSmRNAGene
53. Other pathways regulate the activity of enzymesCopyright
54. Fig. 11-15ReceptionTransductionResponseBinding of epinephrine to G protein-coupled
55. Signaling pathways can also affect the physical
56. Fig. 11-16RESULTSCONCLUSIONWild-type (shmoos)∆Fus3∆forminShmoo projection formingForminPActinsubunitPPForminForminFus3Phosphory- lation cascade GTPG protein-coupledreceptorMatingfactorGDPFus3Fus3PMicrofilament12345
57. Fig. 11-16aRESULTSWild-type (shmoos)∆Fus3∆formin
58. Fig. 11-16bCONCLUSIONMatingfactorG protein-coupledreceptorGDPGTPPhosphory- lation cascadeShmoo projectionformingFus3Fus3Fus3ForminForminPPPForminPActinsubunitMicrofilament12345
59. Fine-Tuning of the ResponseMultistep pathways have two
60. Signal AmplificationEnzyme cascades amplify the cell’s responseAt
61. The Specificity of Cell Signaling and Coordination
62. Fig. 11-17SignalingmoleculeReceptorRelaymoleculesResponse 1Cell A. Pathway leadsto a
63. Fig. 11-17aSignalingmoleculeReceptorRelaymoleculesResponse 1Cell A. Pathway leadsto a
64. Fig. 11-17bResponse 4Response 5Activationor inhibitionCell C. Cross-talk
65. Signaling Efficiency: Scaffolding Proteins and Signaling ComplexesScaffolding
66. Fig. 11-18SignalingmoleculeReceptorScaffoldingproteinPlasmamembraneThreedifferentproteinkinases
67. Termination of the SignalInactivation mechanisms are an
68. Concept 11.5: Apoptosis (programmed cell death) integrates
69. Fig. 11-192 µm
70. Apoptosis in the Soil Worm Caenorhabditis elegansApoptosis
71. Fig. 11-20Ced-9protein (active)inhibits Ced-4activityMitochondrionReceptorfor death-signalingmoleculeCed-4Ced-3Inactive proteins(a) No death signalCed-9(inactive)CellformsblebsDeath-signalingmoleculeOtherproteasesActiveCed-4ActiveCed-3NucleasesActivationcascade(b) Death signal
72. Fig. 11-20aCed-9protein (active)inhibits Ced-4activityMitochondrionCed-4Ced-3Receptorfor death-signalingmoleculeInactive proteins(a) No death signal
73. Fig. 11-20b(b) Death signalDeath-signalingmoleculeCed-9(inactive)CellformsblebsActiveCed-4ActiveCed-3ActivationcascadeOtherproteasesNucleases
74. Apoptotic Pathways and the Signals That Trigger
75. Apoptosis evolved early in animal evolution and
76. Fig. 11-21Interdigital tissue1 mm
77. Fig. 11-UN1ReceptionTransductionResponseReceptorRelay moleculesSignalingmoleculeActivationof cellularresponse123
78. Fig. 11-UN2
79. You should now be able to:Describe the
80. Define the term second messenger; briefly describe
81. Скачать презентанцию

Overview: The Cellular InternetCell-to-cell communication is essential for multicellular organismsBiologists have discovered some universal mechanisms of cellular regulationThe combined effects of multiple signals determine cell responseFor example, the dilation of blood

Слайды и текст этой презентации

Слайд 1Chapter 11
Cell Communication

Слайд 2Overview: The Cellular Internet
Cell-to-cell communication is essential for multicellular organisms
Biologists

have discovered some universal mechanisms of cellular regulation
The combined effects

of multiple signals determine cell response
For example, the dilation of blood vessels is controlled by multiple molecules

Overview: The Cellular InternetCell-to-cell communication is essential for multicellular organismsBiologists have discovered some universal mechanisms of cellular

Слайд 3Fig. 11-1

Слайд 4Concept 11.1: External signals are converted to responses within the

cell
Microbes are a window on the role of cell signaling

in the evolution of life

Concept 11.1: External signals are converted to responses within the cellMicrobes are a window on the role

Слайд 5Evolution of Cell Signaling
A signal transduction pathway is a series

of steps by which a signal on a cell’s surface

is converted into a specific cellular response
Signal transduction pathways convert signals on a cell’s surface into cellular responses

Evolution of Cell SignalingA signal transduction pathway is a series of steps by which a signal on

Слайд 6Fig. 11-2
Receptor
 factor
a factor
a


a
Exchange
of mating
factors
Yeast cell,
mating type a
Yeast cell,
mating type


Mating
New a/
cell
a/
1
2
3

Слайд 7Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes

and were modified later in eukaryotes
The concentration of signaling molecules

allows bacteria to detect population density

Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotesThe concentration

Слайд 8Fig. 11-3
Individual rod-
shaped cells
Spore-forming
structure
(fruiting body)
Aggregation in
process
Fruiting bodies
0.5 mm
1
3
2

Слайд 9Local and Long-Distance Signaling
Cells in a multicellular organism communicate by

chemical messengers
Animal and plant cells have cell junctions that directly

connect the cytoplasm of adjacent cells
In local signaling, animal cells may communicate by direct contact, or cell-cell recognition

Local and Long-Distance SignalingCells in a multicellular organism communicate by chemical messengersAnimal and plant cells have cell

Слайд 10Fig. 11-4
Plasma membranes
Gap junctions
between animal cells
(a) Cell junctions
Plasmodesmata
between plant cells
(b)

Cell-cell recognition

Слайд 11In many other cases, animal cells communicate using local regulators,

messenger molecules that travel only short distances
In long-distance signaling, plants

and animals use chemicals called hormones

In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distancesIn

Слайд 12Fig. 11-5
Local signaling
Target cell
Secreting
cell
Secretory
vesicle
Local regulator
diffuses through
extracellular fluid
(a) Paracrine signaling
(b) Synaptic

signaling
Target cell
is stimulated
Neurotransmitter
diffuses across
synapse
Electrical signal
along nerve

cell
triggers release of
neurotransmitter

Long-distance signaling

Endocrine cell

Blood
vessel

Hormone travels
in bloodstream
to target cells

Target
cell

Слайд 13Fig. 11-5ab
Local signaling
Target cell
Secretory
vesicle
Secreting
cell
Local regulator
diffuses through
extracellular fluid
(a) Paracrine signaling
(b) Synaptic

signaling
Target cell
is stimulated
Neurotransmitter
diffuses across
synapse
Electrical signal
along nerve

cell
triggers release of
neurotransmitter

Fig. 11-5abLocal signalingTarget cellSecretoryvesicleSecretingcellLocal regulatordiffuses throughextracellular fluid(a) Paracrine signaling(b) Synaptic signalingTarget cellis stimulatedNeurotransmitter diffuses across

Слайд 14Fig. 11-5c
Long-distance signaling
Endocrine cell
Blood
vessel
Hormone travels
in bloodstream
to target cells
Target
cell
(c) Hormonal signaling

Fig. 11-5cLong-distance signalingEndocrine cellBloodvesselHormone travelsin bloodstreamto target cellsTargetcell(c) Hormonal signaling

Слайд 15The Three Stages of Cell Signaling: A Preview
Earl W. Sutherland

discovered how the hormone epinephrine acts on cells
Sutherland suggested that

cells receiving signals went through three processes:
Reception
Transduction
Response

Animation: Overview of Cell Signaling

The Three Stages of Cell Signaling: A PreviewEarl W. Sutherland discovered how the hormone epinephrine acts on

Слайд 16Fig. 11-6-1
Reception
1
EXTRACELLULAR
FLUID
Signaling
molecule
Plasma membrane
CYTOPLASM
1
Receptor

Слайд 17Fig. 11-6-2
1
EXTRACELLULAR
FLUID
Signaling
molecule
Plasma membrane
CYTOPLASM
Transduction
2
Relay molecules in a signal transduction pathway
Reception
1
Receptor

Fig. 11-6-21EXTRACELLULARFLUIDSignalingmoleculePlasma membraneCYTOPLASMTransduction2Relay molecules in a signal transduction pathwayReception1Receptor

Слайд 18Fig. 11-6-3
EXTRACELLULAR
FLUID
Plasma membrane
CYTOPLASM
Receptor
Signaling
molecule
Relay molecules in a signal transduction pathway
Activation
of cellular
response
Transduction
Response
2
3
Reception
1

Fig. 11-6-3EXTRACELLULARFLUIDPlasma membraneCYTOPLASMReceptorSignalingmoleculeRelay molecules in a signal transduction pathwayActivationof cellularresponseTransductionResponse23Reception1

Слайд 19Concept 11.2: Reception: A signal molecule binds to a receptor

protein, causing it to change shape
The binding between a signal

molecule (ligand) and receptor is highly specific
A shape change in a receptor is often the initial transduction of the signal
Most signal receptors are plasma membrane proteins

Concept 11.2: Reception: A signal molecule binds to a receptor protein, causing it to change shapeThe binding

Слайд 20Receptors in the Plasma Membrane
Most water-soluble signal molecules bind to

specific sites on receptor proteins in the plasma membrane
There are

three main types of membrane receptors:
G protein-coupled receptors
Receptor tyrosine kinases
Ion channel receptors

Receptors in the Plasma MembraneMost water-soluble signal molecules bind to specific sites on receptor proteins in the

Слайд 21A G protein-coupled receptor is a plasma membrane receptor that

works with the help of a G protein
The G protein

acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive

A G protein-coupled receptor is a plasma membrane receptor that works with the help of a G

Слайд 22Fig. 11-7a
Signaling-molecule binding site
Segment that
interacts with
G proteins
G protein-coupled receptor

Слайд 23Fig. 11-7b
G protein-coupled
receptor
Plasma
membrane
Enzyme
G protein
(inactive)
GDP
CYTOPLASM
Activated
enzyme
GTP
Cellular response
GDP
P
i
Activated
receptor
GDP
GTP
Signaling molecule
Inactive
enzyme
1
2
3
4

Fig. 11-7bG protein-coupledreceptorPlasmamembraneEnzymeG protein(inactive)GDPCYTOPLASMActivatedenzymeGTPCellular responseGDPPiActivatedreceptorGDPGTPSignaling moleculeInactiveenzyme1234

Слайд 24Receptor tyrosine kinases are membrane receptors that attach phosphates to

tyrosines
A receptor tyrosine kinase can trigger multiple signal transduction pathways

at once

Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosinesA receptor tyrosine kinase can trigger multiple

Слайд 25Fig. 11-7c
Signaling
molecule (ligand)
Ligand-binding site
 Helix
Tyrosines
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
CYTOPLASM
Signaling
molecule
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Dimer
Activated relay
proteins
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
P
P
P
P
P
P
Cellular
response 1
Cellular
response 2
Inactive
relay

proteins
Activated tyrosine
kinase regions
Fully activated receptor
tyrosine kinase
6
6 ADP
ATP
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
P
P
P
P
P
P
1
2
3
4

Fig. 11-7cSignalingmolecule (ligand)Ligand-binding site HelixTyrosinesTyrTyrTyrTyrTyrTyrReceptor tyrosinekinase proteinsCYTOPLASMSignalingmoleculeTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrDimerActivated relayproteinsTyrTyrTyrTyrTyrTyrPPPPPPCellularresponse 1Cellularresponse 2Inactiverelay proteinsActivated tyrosinekinase regionsFully activated receptortyrosine kinase66 ADPATPTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrPPPPPP1234

Слайд 26A ligand-gated ion channel receptor acts as a gate when

the receptor changes shape
When a signal molecule binds as a

ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor

A ligand-gated ion channel receptor acts as a gate when the receptor changes shapeWhen a signal molecule

Слайд 27Fig. 11-7d
Signaling
molecule
(ligand)
Gate
closed
Ions
Ligand-gated
ion channel receptor
Plasma
membrane
Gate open
Cellular
response
Gate closed
3
2
1

Fig. 11-7dSignalingmolecule(ligand)GateclosedIonsLigand-gatedion channel receptorPlasmamembraneGate openCellularresponseGate closed321

Слайд 28Intracellular Receptors
Some receptor proteins are intracellular, found in the cytosol

or nucleus of target cells
Small or hydrophobic chemical messengers can

readily cross the membrane and activate receptors
Examples of hydrophobic messengers are the steroid and thyroid hormones of animals
An activated hormone-receptor complex can act as a transcription factor, turning on specific genes

Intracellular ReceptorsSome receptor proteins are intracellular, found in the cytosol or nucleus of target cellsSmall or hydrophobic

Слайд 29Fig. 11-8-1
Hormone
(testosterone)
Receptor
protein
Plasma
membrane
EXTRACELLULAR
FLUID
DNA
NUCLEUS
CYTOPLASM

Слайд 30Fig. 11-8-2
Receptor
protein
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Hormone-
receptor
complex
DNA
NUCLEUS
CYTOPLASM

Fig. 11-8-2ReceptorproteinHormone(testosterone)EXTRACELLULARFLUIDPlasmamembraneHormone-receptorcomplexDNANUCLEUSCYTOPLASM

Слайд 31Fig. 11-8-3
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Receptor
protein
Plasma
membrane
Hormone-
receptor
complex
DNA
NUCLEUS
CYTOPLASM

Fig. 11-8-3Hormone(testosterone)EXTRACELLULARFLUIDReceptorproteinPlasmamembraneHormone-receptorcomplexDNANUCLEUSCYTOPLASM

Слайд 32Fig. 11-8-4
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormone-
receptor
complex
DNA
mRNA
NUCLEUS
CYTOPLASM

Fig. 11-8-4Hormone(testosterone)EXTRACELLULARFLUIDPlasmamembraneReceptorproteinHormone-receptorcomplexDNAmRNANUCLEUSCYTOPLASM

Слайд 33Fig. 11-8-5
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Receptor
protein
Plasma
membrane
Hormone-
receptor
complex
DNA
mRNA
NUCLEUS
New protein
CYTOPLASM

Fig. 11-8-5Hormone(testosterone)EXTRACELLULARFLUIDReceptorproteinPlasmamembraneHormone-receptorcomplexDNAmRNANUCLEUSNew proteinCYTOPLASM

Слайд 34Concept 11.3: Transduction: Cascades of molecular interactions relay signals from

receptors to target molecules in the cell
Signal transduction usually involves

multiple steps
Multistep pathways can amplify a signal: A few molecules can produce a large cellular response
Multistep pathways provide more opportunities for coordination and regulation of the cellular response

Concept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cellSignal

Слайд 35Signal Transduction Pathways
The molecules that relay a signal from receptor

to response are mostly proteins
Like falling dominoes, the receptor activates

another protein, which activates another, and so on, until the protein producing the response is activated
At each step, the signal is transduced into a different form, usually a shape change in a protein

Signal Transduction PathwaysThe molecules that relay a signal from receptor to response are mostly proteinsLike falling dominoes,

Слайд 36Protein Phosphorylation and Dephosphorylation
In many pathways, the signal is transmitted

by a cascade of protein phosphorylations
Protein kinases transfer phosphates from

ATP to protein, a process called phosphorylation

Protein Phosphorylation and DephosphorylationIn many pathways, the signal is transmitted by a cascade of protein phosphorylationsProtein kinases

Слайд 37Protein phosphatases remove the phosphates from proteins, a process called

dephosphorylation
This phosphorylation and dephosphorylation system acts as a molecular switch,

turning activities on and off

Protein phosphatases remove the phosphates from proteins, a process called dephosphorylationThis phosphorylation and dephosphorylation system acts as

Слайд 38Fig. 11-9
Signaling molecule
Receptor
Activated relay
molecule
Inactive
protein kinase
1
Active
protein
kinase
1
Inactive
protein kinase
2
ATP
ADP
Active
protein
kinase
2
P
P
PP
Inactive
protein kinase
3
ATP
ADP
Active
protein
kinase
3
P
P
PP
i
ATP
ADP
P
Active
protein
PP
P
i
Inactive
protein
Cellular
response
Phosphorylation cascade
i

Fig. 11-9Signaling moleculeReceptorActivated relaymoleculeInactiveprotein kinase1Activeproteinkinase1Inactiveprotein kinase2ATPADPActiveproteinkinase2PPPPInactiveprotein kinase3ATPADPActiveproteinkinase3PPPPiATPADPPActiveproteinPPPiInactiveproteinCellularresponsePhosphorylation cascadei

Слайд 39Small Molecules and Ions as Second Messengers
The extracellular signal molecule

that binds to the receptor is a pathway’s “first messenger”
Second

messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion
Second messengers participate in pathways initiated by G protein-coupled receptors and receptor tyrosine kinases
Cyclic AMP and calcium ions are common second messengers

Small Molecules and Ions as Second MessengersThe extracellular signal molecule that binds to the receptor is a

Слайд 40Cyclic AMP
Cyclic AMP (cAMP) is one of the most widely

used second messengers
Adenylyl cyclase, an enzyme in the plasma membrane,

converts ATP to cAMP in response to an extracellular signal

Cyclic AMPCyclic AMP (cAMP) is one of the most widely used second messengersAdenylyl cyclase, an enzyme in

Слайд 41Adenylyl cyclase
Fig. 11-10
Pyrophosphate
P
P
i
ATP
cAMP
Phosphodiesterase
AMP

Слайд 42Many signal molecules trigger formation of cAMP
Other components of cAMP

pathways are G proteins, G protein-coupled receptors, and protein kinases
cAMP

usually activates protein kinase A, which phosphorylates various other proteins
Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase

Many signal molecules trigger formation of cAMPOther components of cAMP pathways are G proteins, G protein-coupled receptors,

Слайд 43First messenger
Fig. 11-11
G protein
Adenylyl
cyclase
GTP
ATP
cAMP
Second
messenger
Protein
kinase A
G protein-coupled
receptor
Cellular responses

First messengerFig. 11-11G proteinAdenylylcyclaseGTPATPcAMPSecondmessengerProteinkinase AG protein-coupledreceptorCellular responses

Слайд 44Calcium Ions and Inositol Triphosphate (IP3)
Calcium ions (Ca2+) act as

a second messenger in many pathways
Calcium is an important second

messenger because cells can regulate its concentration

Calcium Ions and Inositol Triphosphate (IP3)Calcium ions (Ca2+) act as a second messenger in many pathwaysCalcium is

Слайд 45EXTRACELLULAR
FLUID
Fig. 11-12
ATP
Nucleus
Mitochondrion
Ca2+ pump
Plasma
membrane
CYTOSOL
Ca2+
pump
Endoplasmic
reticulum (ER)
Ca2+
pump
ATP
Key
High [Ca2+]
Low [Ca2+]

EXTRACELLULARFLUIDFig. 11-12ATPNucleusMitochondrionCa2+ pumpPlasmamembraneCYTOSOLCa2+pumpEndoplasmicreticulum (ER)Ca2+pumpATPKeyHigh [Ca2+]Low [Ca2+]

Слайд 46A signal relayed by a signal transduction pathway may trigger

an increase in calcium in the cytosol
Pathways leading to the

release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers

Animation: Signal Transduction Pathways

A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosolPathways

Слайд 47Fig. 11-13-1
EXTRA-
CELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
GTP
G protein-coupled
receptor
Phospholipase C
PIP2
IP3
DAG
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
Ca2+
CYTOSOL

Fig. 11-13-1EXTRA-CELLULARFLUIDSignaling molecule(first messenger)G proteinGTPG protein-coupledreceptorPhospholipase CPIP2IP3DAG(second messenger)IP3-gatedcalcium channelEndoplasmicreticulum (ER)Ca2+CYTOSOL

Слайд 48Fig. 11-13-2
G protein
EXTRA-
CELLULAR
FLUID
Signaling molecule
(first messenger)
G protein-coupled
receptor
Phospholipase C
PIP2
DAG
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
Ca2+
CYTOSOL
Ca2+
(second
messenger)
GTP

Fig. 11-13-2G proteinEXTRA-CELLULARFLUIDSignaling molecule(first messenger)G protein-coupledreceptorPhospholipase CPIP2DAGIP3(second messenger)IP3-gatedcalcium channelEndoplasmicreticulum (ER)Ca2+CYTOSOLCa2+(secondmessenger)GTP

Слайд 49Fig. 11-13-3
G protein
EXTRA-
CELLULAR
FLUID
Signaling molecule
(first messenger)
G protein-coupled
receptor
Phospholipase C
PIP2
DAG
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
Ca2+
CYTOSOL
Various
proteins
activated
Cellular
responses
Ca2+
(second
messenger)
GTP

Fig. 11-13-3G proteinEXTRA-CELLULARFLUIDSignaling molecule(first messenger)G protein-coupledreceptorPhospholipase CPIP2DAGIP3(second messenger)IP3-gatedcalcium channelEndoplasmicreticulum (ER)Ca2+CYTOSOLVariousproteinsactivatedCellularresponsesCa2+(secondmessenger)GTP

Слайд 50Concept 11.4: Response: Cell signaling leads to regulation of transcription

or cytoplasmic activities
The cell’s response to an extracellular signal is

sometimes called the “output response”

Concept 11.4: Response: Cell signaling leads to regulation of transcription or cytoplasmic activitiesThe cell’s response to an

Слайд 51Nuclear and Cytoplasmic Responses
Ultimately, a signal transduction pathway leads to

regulation of one or more cellular activities
The response may occur

in the cytoplasm or may involve action in the nucleus
Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus
The final activated molecule may function as a transcription factor

Nuclear and Cytoplasmic ResponsesUltimately, a signal transduction pathway leads to regulation of one or more cellular activitiesThe

Слайд 52Fig. 11-14
Growth factor
Receptor
Phosphorylation
cascade
Reception
Transduction
Active
transcription
factor
Response
P
Inactive
transcription
factor
CYTOPLASM
DNA
NUCLEUS
mRNA
Gene

Fig. 11-14Growth factorReceptorPhosphorylationcascadeReceptionTransductionActivetranscriptionfactorResponsePInactivetranscriptionfactorCYTOPLASMDNANUCLEUSmRNAGene

Слайд 53Other pathways regulate the activity of enzymes

Copyright © 2008 Pearson

Education, Inc., publishing as Pearson Benjamin Cummings

Слайд 54Fig. 11-15
Reception
Transduction
Response
Binding of epinephrine to G protein-coupled receptor (1 molecule)
Inactive

G protein
Active G protein (102 molecules)
Inactive adenylyl cyclase
Active adenylyl cyclase

(102)

ATP

Cyclic AMP (104)

Inactive protein kinase A

Active protein kinase A (104)

Inactive phosphorylase kinase

Active phosphorylase kinase (105)

Inactive glycogen phosphorylase

Active glycogen phosphorylase (106)

Glycogen

Glucose-1-phosphate
(108 molecules)

Fig. 11-15ReceptionTransductionResponseBinding of epinephrine to G protein-coupled receptor (1 molecule)Inactive G proteinActive G protein (102 molecules)Inactive adenylyl

Слайд 55Signaling pathways can also affect the physical characteristics of a

cell, for example, cell shape
Copyright © 2008 Pearson Education, Inc.,

publishing as Pearson Benjamin Cummings

Signaling pathways can also affect the physical characteristics of a cell, for example, cell shapeCopyright © 2008

Слайд 56Fig. 11-16
RESULTS
CONCLUSION
Wild-type (shmoos)
∆Fus3
∆formin
Shmoo projection forming
Formin
P
Actin
subunit
P
P
Formin
Formin
Fus3
Phosphory-
lation
cascade

GTP
G protein-coupled
receptor
Mating
factor
GDP
Fus3
Fus3
P
Microfilament
1
2
3
4
5

Fig. 11-16RESULTSCONCLUSIONWild-type (shmoos)∆Fus3∆forminShmoo projection formingForminPActinsubunitPPForminForminFus3Phosphory- lation cascade GTPG protein-coupledreceptorMatingfactorGDPFus3Fus3PMicrofilament12345

Слайд 57Fig. 11-16a
RESULTS
Wild-type (shmoos)
∆Fus3
∆formin

Слайд 58Fig. 11-16b
CONCLUSION
Mating
factor
G protein-coupled
receptor
GDP
GTP
Phosphory-
lation
cascade
Shmoo projection
forming
Fus3
Fus3
Fus3
Formin
Formin
P
P
P
Formin
P
Actin
subunit
Microfilament
1
2
3
4
5

Fig. 11-16bCONCLUSIONMatingfactorG protein-coupledreceptorGDPGTPPhosphory- lation cascadeShmoo projectionformingFus3Fus3Fus3ForminForminPPPForminPActinsubunitMicrofilament12345

Слайд 59Fine-Tuning of the Response
Multistep pathways have two important benefits:
Amplifying the

signal (and thus the response)
Contributing to the specificity of the

response

Слайд 60Signal Amplification
Enzyme cascades amplify the cell’s response
At each step, the

number of activated products is much greater than in the

preceding step

Signal AmplificationEnzyme cascades amplify the cell’s responseAt each step, the number of activated products is much greater

Слайд 61The Specificity of Cell Signaling and Coordination of the Response
Different

kinds of cells have different collections of proteins
These different proteins

allow cells to detect and respond to different signals
Even the same signal can have different effects in cells with different proteins and pathways
Pathway branching and “cross-talk” further help the cell coordinate incoming signals

The Specificity of Cell Signaling and Coordination of the ResponseDifferent kinds of cells have different collections of

Слайд 62Fig. 11-17
Signaling
molecule
Receptor
Relay
molecules
Response 1
Cell A. Pathway leads
to a single response.
Response 2
Response

3
Cell B. Pathway branches,
leading to two responses.
Response 4
Response 5
Activation
or inhibition
Cell

C. Cross-talk occurs
between two pathways.

Cell D. Different receptor
leads to a different response.

Fig. 11-17SignalingmoleculeReceptorRelaymoleculesResponse 1Cell A. Pathway leadsto a single response.Response 2Response 3Cell B. Pathway branches,leading to two responses.Response

Слайд 63Fig. 11-17a
Signaling
molecule
Receptor
Relay
molecules
Response 1
Cell A. Pathway leads
to a single response.
Cell B.

Pathway branches,
leading to two responses.
Response 2
Response 3

Fig. 11-17aSignalingmoleculeReceptorRelaymoleculesResponse 1Cell A. Pathway leadsto a single response.Cell B. Pathway branches,leading to two responses.Response 2Response 3

Слайд 64Fig. 11-17b
Response 4
Response 5
Activation
or inhibition
Cell C. Cross-talk occurs
between two pathways.
Cell

D. Different receptor
leads to a different response.

Fig. 11-17bResponse 4Response 5Activationor inhibitionCell C. Cross-talk occursbetween two pathways.Cell D. Different receptorleads to a different response.

Слайд 65Signaling Efficiency: Scaffolding Proteins and Signaling Complexes
Scaffolding proteins are large

relay proteins to which other relay proteins are attached
Scaffolding proteins

can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway

Signaling Efficiency: Scaffolding Proteins and Signaling ComplexesScaffolding proteins are large relay proteins to which other relay proteins

Слайд 66Fig. 11-18
Signaling
molecule
Receptor
Scaffolding
protein
Plasma
membrane
Three
different
protein
kinases

Слайд 67Termination of the Signal
Inactivation mechanisms are an essential aspect of

cell signaling
When signal molecules leave the receptor, the receptor reverts

to its inactive state

Termination of the SignalInactivation mechanisms are an essential aspect of cell signalingWhen signal molecules leave the receptor,

Слайд 68Concept 11.5: Apoptosis (programmed cell death) integrates multiple cell-signaling pathways
Apoptosis

is programmed or controlled cell suicide
A cell is chopped and

packaged into vesicles that are digested by scavenger cells
Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells

Concept 11.5: Apoptosis (programmed cell death) integrates multiple cell-signaling pathwaysApoptosis is programmed or controlled cell suicideA cell

Слайд 69Fig. 11-19
2 µm

Слайд 70Apoptosis in the Soil Worm Caenorhabditis elegans
Apoptosis is important in

shaping an organism during embryonic development
The role of apoptosis in

embryonic development was first studied in Caenorhabditis elegans
In C. elegans, apoptosis results when specific proteins that “accelerate” apoptosis override those that “put the brakes” on apoptosis

Apoptosis in the Soil Worm Caenorhabditis elegansApoptosis is important in shaping an organism during embryonic developmentThe role

Слайд 71Fig. 11-20
Ced-9
protein (active)
inhibits Ced-4
activity
Mitochondrion
Receptor
for death-
signaling
molecule
Ced-4
Ced-3
Inactive proteins
(a) No death signal
Ced-9
(inactive)
Cell
forms
blebs
Death-
signaling
molecule
Other
proteases
Active
Ced-4
Active
Ced-3
Nucleases
Activation
cascade
(b) Death

signal

Слайд 72Fig. 11-20a
Ced-9
protein (active)
inhibits Ced-4
activity
Mitochondrion
Ced-4
Ced-3
Receptor
for death-
signaling
molecule
Inactive proteins
(a) No death signal

Fig. 11-20aCed-9protein (active)inhibits Ced-4activityMitochondrionCed-4Ced-3Receptorfor death-signalingmoleculeInactive proteins(a) No death signal

Слайд 73Fig. 11-20b
(b) Death signal
Death-
signaling
molecule
Ced-9
(inactive)
Cell
forms
blebs
Active
Ced-4
Active
Ced-3
Activation
cascade
Other
proteases
Nucleases

Fig. 11-20b(b) Death signalDeath-signalingmoleculeCed-9(inactive)CellformsblebsActiveCed-4ActiveCed-3ActivationcascadeOtherproteasesNucleases

Слайд 74Apoptotic Pathways and the Signals That Trigger Them
Caspases are the

main proteases (enzymes that cut up proteins) that carry out

apoptosis
Apoptosis can be triggered by:
An extracellular death-signaling ligand
DNA damage in the nucleus
Protein misfolding in the endoplasmic reticulum

Apoptotic Pathways and the Signals That Trigger ThemCaspases are the main proteases (enzymes that cut up proteins)

Слайд 75Apoptosis evolved early in animal evolution and is essential for

the development and maintenance of all animals
Apoptosis may be involved

in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers

Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animalsApoptosis

Слайд 76Fig. 11-21
Interdigital tissue
1 mm

Слайд 77Fig. 11-UN1
Reception
Transduction
Response
Receptor
Relay molecules
Signaling
molecule
Activation
of cellular
response
1
2
3

Слайд 78Fig. 11-UN2

Слайд 79You should now be able to:
Describe the nature of a

ligand-receptor interaction and state how such interactions initiate a signal-transduction

system
Compare and contrast G protein-coupled receptors, tyrosine kinase receptors, and ligand-gated ion channels
List two advantages of a multistep pathway in the transduction stage of cell signaling
Explain how an original signal molecule can produce a cellular response when it may not even enter the target cell

You should now be able to:Describe the nature of a ligand-receptor interaction and state how such interactions

Слайд 80Define the term second messenger; briefly describe the role of

these molecules in signaling pathways
Explain why different types of cells

may respond differently to the same signal molecule
Describe the role of apoptosis in normal development and degenerative disease in vertebrates

Define the term second messenger; briefly describe the role of these molecules in signaling pathwaysExplain why different

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Chapter 11

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Слайд 1Chapter 11Cell Communication

Слайд 2Overview: The Cellular InternetCell-to-cell communication is essential for multicellular organismsBiologists

have discovered some universal mechanisms of cellular regulationThe combined effects

Слайд 3Fig. 11-1

Слайд 4Concept 11.1: External signals are converted to responses within the

cellMicrobes are a window on the role of cell signaling

Слайд 5Evolution of Cell SignalingA signal transduction pathway is a series

of steps by which a signal on a cell’s surface

Слайд 6Fig. 11-2Receptor factora factoraaExchangeof matingfactorsYeast cell,mating type aYeast cell,mating type

MatingNew a/cella/123

Слайд 7Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes

and were modified later in eukaryotesThe concentration of signaling molecules

Слайд 8Fig. 11-3Individual rod-shaped cellsSpore-formingstructure(fruiting body)Aggregation inprocessFruiting bodies0.5 mm132

Слайд 9Local and Long-Distance SignalingCells in a multicellular organism communicate by

chemical messengersAnimal and plant cells have cell junctions that directly

Слайд 10Fig. 11-4Plasma membranesGap junctionsbetween animal cells(a) Cell junctionsPlasmodesmatabetween plant cells(b)

Cell-cell recognition

Слайд 11In many other cases, animal cells communicate using local regulators,

messenger molecules that travel only short distancesIn long-distance signaling, plants

Слайд 12Fig. 11-5Local signalingTarget cellSecretingcellSecretoryvesicleLocal regulatordiffuses throughextracellular fluid(a) Paracrine signaling(b) Synaptic

signalingTarget cellis stimulatedNeurotransmitter diffuses across synapseElectrical signalalong nerve

Слайд 13Fig. 11-5abLocal signalingTarget cellSecretoryvesicleSecretingcellLocal regulatordiffuses throughextracellular fluid(a) Paracrine signaling(b) Synaptic

signalingTarget cellis stimulatedNeurotransmitter diffuses across synapseElectrical signalalong nerve

Слайд 14Fig. 11-5cLong-distance signalingEndocrine cellBloodvesselHormone travelsin bloodstreamto target cellsTargetcell(c) Hormonal signaling

Слайд 15The Three Stages of Cell Signaling: A PreviewEarl W. Sutherland

discovered how the hormone epinephrine acts on cellsSutherland suggested that

Слайд 16Fig. 11-6-1Reception1EXTRACELLULARFLUIDSignalingmoleculePlasma membraneCYTOPLASM1Receptor

Слайд 17Fig. 11-6-21EXTRACELLULARFLUIDSignalingmoleculePlasma membraneCYTOPLASMTransduction2Relay molecules in a signal transduction pathwayReception1Receptor

Слайд 18Fig. 11-6-3EXTRACELLULARFLUIDPlasma membraneCYTOPLASMReceptorSignalingmoleculeRelay molecules in a signal transduction pathwayActivationof cellularresponseTransductionResponse23Reception1

Слайд 19Concept 11.2: Reception: A signal molecule binds to a receptor

protein, causing it to change shapeThe binding between a signal

Слайд 20Receptors in the Plasma MembraneMost water-soluble signal molecules bind to

specific sites on receptor proteins in the plasma membraneThere are

Слайд 21A G protein-coupled receptor is a plasma membrane receptor that

works with the help of a G proteinThe G protein

Слайд 22Fig. 11-7aSignaling-molecule binding siteSegment thatinteracts withG proteinsG protein-coupled receptor

Слайд 23Fig. 11-7bG protein-coupledreceptorPlasmamembraneEnzymeG protein(inactive)GDPCYTOPLASMActivatedenzymeGTPCellular responseGDPPiActivatedreceptorGDPGTPSignaling moleculeInactiveenzyme1234

Слайд 24Receptor tyrosine kinases are membrane receptors that attach phosphates to

tyrosinesA receptor tyrosine kinase can trigger multiple signal transduction pathways

Слайд 25Fig. 11-7cSignalingmolecule (ligand)Ligand-binding site HelixTyrosinesTyrTyrTyrTyrTyrTyrReceptor tyrosinekinase proteinsCYTOPLASMSignalingmoleculeTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrDimerActivated relayproteinsTyrTyrTyrTyrTyrTyrPPPPPPCellularresponse 1Cellularresponse 2Inactiverelay

proteinsActivated tyrosinekinase regionsFully activated receptortyrosine kinase66 ADPATPTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrTyrPPPPPP1234

Слайд 26A ligand-gated ion channel receptor acts as a gate when

the receptor changes shapeWhen a signal molecule binds as a

Слайд 27Fig. 11-7dSignalingmolecule(ligand)GateclosedIonsLigand-gatedion channel receptorPlasmamembraneGate openCellularresponseGate closed321

Слайд 28Intracellular ReceptorsSome receptor proteins are intracellular, found in the cytosol

or nucleus of target cellsSmall or hydrophobic chemical messengers can

Слайд 29Fig. 11-8-1Hormone(testosterone)ReceptorproteinPlasmamembraneEXTRACELLULARFLUIDDNANUCLEUSCYTOPLASM

Слайд 30Fig. 11-8-2ReceptorproteinHormone(testosterone)EXTRACELLULARFLUIDPlasmamembraneHormone-receptorcomplexDNANUCLEUSCYTOPLASM

Слайд 31Fig. 11-8-3Hormone(testosterone)EXTRACELLULARFLUIDReceptorproteinPlasmamembraneHormone-receptorcomplexDNANUCLEUSCYTOPLASM

Слайд 32Fig. 11-8-4Hormone(testosterone)EXTRACELLULARFLUIDPlasmamembraneReceptorproteinHormone-receptorcomplexDNAmRNANUCLEUSCYTOPLASM

Слайд 33Fig. 11-8-5Hormone(testosterone)EXTRACELLULARFLUIDReceptorproteinPlasmamembraneHormone-receptorcomplexDNAmRNANUCLEUSNew proteinCYTOPLASM

Слайд 34Concept 11.3: Transduction: Cascades of molecular interactions relay signals from

receptors to target molecules in the cellSignal transduction usually involves

Слайд 35Signal Transduction PathwaysThe molecules that relay a signal from receptor

to response are mostly proteinsLike falling dominoes, the receptor activates

Слайд 36Protein Phosphorylation and DephosphorylationIn many pathways, the signal is transmitted

by a cascade of protein phosphorylationsProtein kinases transfer phosphates from

Слайд 37Protein phosphatases remove the phosphates from proteins, a process called

dephosphorylationThis phosphorylation and dephosphorylation system acts as a molecular switch,

Слайд 39Small Molecules and Ions as Second MessengersThe extracellular signal molecule

that binds to the receptor is a pathway’s “first messenger”Second

Слайд 40Cyclic AMPCyclic AMP (cAMP) is one of the most widely

used second messengersAdenylyl cyclase, an enzyme in the plasma membrane,

Слайд 41Adenylyl cyclaseFig. 11-10PyrophosphatePPiATPcAMPPhosphodiesteraseAMP

Слайд 42Many signal molecules trigger formation of cAMPOther components of cAMP

pathways are G proteins, G protein-coupled receptors, and protein kinasescAMP

Слайд 43First messengerFig. 11-11G proteinAdenylylcyclaseGTPATPcAMPSecondmessengerProteinkinase AG protein-coupledreceptorCellular responses

Слайд 44Calcium Ions and Inositol Triphosphate (IP3)Calcium ions (Ca2+) act as

a second messenger in many pathwaysCalcium is an important second

Слайд 45EXTRACELLULARFLUIDFig. 11-12ATPNucleusMitochondrionCa2+ pumpPlasmamembraneCYTOSOLCa2+pumpEndoplasmicreticulum (ER)Ca2+pumpATPKeyHigh [Ca2+]Low [Ca2+]

Слайд 46A signal relayed by a signal transduction pathway may trigger

an increase in calcium in the cytosolPathways leading to the

Слайд 47Fig. 11-13-1EXTRA-CELLULARFLUIDSignaling molecule(first messenger)G proteinGTPG protein-coupledreceptorPhospholipase CPIP2IP3DAG(second messenger)IP3-gatedcalcium channelEndoplasmicreticulum (ER)Ca2+CYTOSOL

Слайд 48Fig. 11-13-2G proteinEXTRA-CELLULARFLUIDSignaling molecule(first messenger)G protein-coupledreceptorPhospholipase CPIP2DAGIP3(second messenger)IP3-gatedcalcium channelEndoplasmicreticulum (ER)Ca2+CYTOSOLCa2+(secondmessenger)GTP

Слайд 49Fig. 11-13-3G proteinEXTRA-CELLULARFLUIDSignaling molecule(first messenger)G protein-coupledreceptorPhospholipase CPIP2DAGIP3(second messenger)IP3-gatedcalcium channelEndoplasmicreticulum (ER)Ca2+CYTOSOLVariousproteinsactivatedCellularresponsesCa2+(secondmessenger)GTP

Слайд 50Concept 11.4: Response: Cell signaling leads to regulation of transcription

Слайд 1Chapter 11
Cell Communication

Слайд 2Overview: The Cellular Internet
Cell-to-cell communication is essential for multicellular organisms
Biologists

have discovered some universal mechanisms of cellular regulation
The combined effects

cell
Microbes are a window on the role of cell signaling

Слайд 5Evolution of Cell Signaling
A signal transduction pathway is a series

Слайд 6Fig. 11-2
Receptor
 factor
a factor
a


a
Exchange
of mating
factors
Yeast cell,
mating type a
Yeast cell,
mating type


Mating
New a/
cell
a/
1
2
3

and were modified later in eukaryotes
The concentration of signaling molecules

Слайд 8Fig. 11-3
Individual rod-
shaped cells
Spore-forming
structure
(fruiting body)
Aggregation in
process
Fruiting bodies
0.5 mm
1
3
2

Слайд 9Local and Long-Distance Signaling
Cells in a multicellular organism communicate by

chemical messengers
Animal and plant cells have cell junctions that directly

Слайд 10Fig. 11-4
Plasma membranes
Gap junctions
between animal cells
(a) Cell junctions
Plasmodesmata
between plant cells
(b)

messenger molecules that travel only short distances
In long-distance signaling, plants

Слайд 12Fig. 11-5
Local signaling
Target cell
Secreting
cell
Secretory
vesicle
Local regulator
diffuses through
extracellular fluid
(a) Paracrine signaling
(b) Synaptic

signaling
Target cell
is stimulated
Neurotransmitter
diffuses across
synapse
Electrical signal
along nerve

Слайд 13Fig. 11-5ab
Local signaling
Target cell
Secretory
vesicle
Secreting
cell
Local regulator
diffuses through
extracellular fluid
(a) Paracrine signaling
(b) Synaptic

signaling
Target cell
is stimulated
Neurotransmitter
diffuses across
synapse
Electrical signal
along nerve

Слайд 14Fig. 11-5c
Long-distance signaling
Endocrine cell
Blood
vessel
Hormone travels
in bloodstream
to target cells
Target
cell
(c) Hormonal signaling

Слайд 15The Three Stages of Cell Signaling: A Preview
Earl W. Sutherland

discovered how the hormone epinephrine acts on cells
Sutherland suggested that

Слайд 16Fig. 11-6-1
Reception
1
EXTRACELLULAR
FLUID
Signaling
molecule
Plasma membrane
CYTOPLASM
1
Receptor

Слайд 17Fig. 11-6-2
1
EXTRACELLULAR
FLUID
Signaling
molecule
Plasma membrane
CYTOPLASM
Transduction
2
Relay molecules in a signal transduction pathway
Reception
1
Receptor

Слайд 18Fig. 11-6-3
EXTRACELLULAR
FLUID
Plasma membrane
CYTOPLASM
Receptor
Signaling
molecule
Relay molecules in a signal transduction pathway
Activation
of cellular
response
Transduction
Response
2
3
Reception
1

protein, causing it to change shape
The binding between a signal

Слайд 20Receptors in the Plasma Membrane
Most water-soluble signal molecules bind to

specific sites on receptor proteins in the plasma membrane
There are

works with the help of a G protein
The G protein

Слайд 22Fig. 11-7a
Signaling-molecule binding site
Segment that
interacts with
G proteins
G protein-coupled receptor

Слайд 23Fig. 11-7b
G protein-coupled
receptor
Plasma
membrane
Enzyme
G protein
(inactive)
GDP
CYTOPLASM
Activated
enzyme
GTP
Cellular response
GDP
P
i
Activated
receptor
GDP
GTP
Signaling molecule
Inactive
enzyme
1
2
3
4

tyrosines
A receptor tyrosine kinase can trigger multiple signal transduction pathways

proteins
Activated tyrosine
kinase regions
Fully activated receptor
tyrosine kinase
6
6 ADP
ATP
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
P
P
P
P
P
P
1
2
3
4

the receptor changes shape
When a signal molecule binds as a

Слайд 27Fig. 11-7d
Signaling
molecule
(ligand)
Gate
closed
Ions
Ligand-gated
ion channel receptor
Plasma
membrane
Gate open
Cellular
response
Gate closed
3
2
1

Слайд 28Intracellular Receptors
Some receptor proteins are intracellular, found in the cytosol

or nucleus of target cells
Small or hydrophobic chemical messengers can

Слайд 29Fig. 11-8-1
Hormone
(testosterone)
Receptor
protein
Plasma
membrane
EXTRACELLULAR
FLUID
DNA
NUCLEUS
CYTOPLASM

Слайд 30Fig. 11-8-2
Receptor
protein
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Hormone-
receptor
complex
DNA
NUCLEUS
CYTOPLASM

Слайд 31Fig. 11-8-3
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Receptor
protein
Plasma
membrane
Hormone-
receptor
complex
DNA
NUCLEUS
CYTOPLASM

Слайд 32Fig. 11-8-4
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormone-
receptor
complex
DNA
mRNA
NUCLEUS
CYTOPLASM

Слайд 33Fig. 11-8-5
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Receptor
protein
Plasma
membrane
Hormone-
receptor
complex
DNA
mRNA
NUCLEUS
New protein
CYTOPLASM

receptors to target molecules in the cell
Signal transduction usually involves

Слайд 35Signal Transduction Pathways
The molecules that relay a signal from receptor

to response are mostly proteins
Like falling dominoes, the receptor activates

Слайд 36Protein Phosphorylation and Dephosphorylation
In many pathways, the signal is transmitted

by a cascade of protein phosphorylations
Protein kinases transfer phosphates from

dephosphorylation
This phosphorylation and dephosphorylation system acts as a molecular switch,

Слайд 39Small Molecules and Ions as Second Messengers
The extracellular signal molecule

that binds to the receptor is a pathway’s “first messenger”
Second

Слайд 40Cyclic AMP
Cyclic AMP (cAMP) is one of the most widely

used second messengers
Adenylyl cyclase, an enzyme in the plasma membrane,

Слайд 41Adenylyl cyclase
Fig. 11-10
Pyrophosphate
P
P
i
ATP
cAMP
Phosphodiesterase
AMP

Слайд 42Many signal molecules trigger formation of cAMP
Other components of cAMP

pathways are G proteins, G protein-coupled receptors, and protein kinases
cAMP

Слайд 43First messenger
Fig. 11-11
G protein
Adenylyl
cyclase
GTP
ATP
cAMP
Second
messenger
Protein
kinase A
G protein-coupled
receptor
Cellular responses

Слайд 44Calcium Ions and Inositol Triphosphate (IP3)
Calcium ions (Ca2+) act as

a second messenger in many pathways
Calcium is an important second

Слайд 45EXTRACELLULAR
FLUID
Fig. 11-12
ATP
Nucleus
Mitochondrion
Ca2+ pump
Plasma
membrane
CYTOSOL
Ca2+
pump
Endoplasmic
reticulum (ER)
Ca2+
pump
ATP
Key
High [Ca2+]
Low [Ca2+]

an increase in calcium in the cytosol
Pathways leading to the

Слайд 47Fig. 11-13-1
EXTRA-
CELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
GTP
G protein-coupled
receptor
Phospholipase C
PIP2
IP3
DAG
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
Ca2+
CYTOSOL

Слайд 48Fig. 11-13-2
G protein
EXTRA-
CELLULAR
FLUID
Signaling molecule
(first messenger)
G protein-coupled
receptor
Phospholipase C
PIP2
DAG
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
Ca2+
CYTOSOL
Ca2+
(second
messenger)
GTP

or cytoplasmic activities
The cell’s response to an extracellular signal is

Слайд 51Nuclear and Cytoplasmic Responses
Ultimately, a signal transduction pathway leads to

regulation of one or more cellular activities
The response may occur

Слайд 52Fig. 11-14
Growth factor
Receptor
Phosphorylation
cascade
Reception
Transduction
Active
transcription
factor
Response
P
Inactive
transcription
factor
CYTOPLASM
DNA
NUCLEUS
mRNA
Gene

Слайд 53Other pathways regulate the activity of enzymes

Copyright © 2008 Pearson

Слайд 54Fig. 11-15
Reception
Transduction
Response
Binding of epinephrine to G protein-coupled receptor (1 molecule)
Inactive

G protein
Active G protein (102 molecules)
Inactive adenylyl cyclase
Active adenylyl cyclase

cell, for example, cell shape
Copyright © 2008 Pearson Education, Inc.,

Слайд 56Fig. 11-16
RESULTS
CONCLUSION
Wild-type (shmoos)
∆Fus3
∆formin
Shmoo projection forming
Formin
P
Actin
subunit
P
P
Formin
Formin
Fus3
Phosphory-
lation
cascade

GTP
G protein-coupled
receptor
Mating
factor
GDP
Fus3
Fus3
P
Microfilament
1
2
3
4
5

Слайд 57Fig. 11-16a
RESULTS
Wild-type (shmoos)
∆Fus3
∆formin

Слайд 58Fig. 11-16b
CONCLUSION
Mating
factor
G protein-coupled
receptor
GDP
GTP
Phosphory-
lation
cascade
Shmoo projection
forming
Fus3
Fus3
Fus3
Formin
Formin
P
P
P
Formin
P
Actin
subunit
Microfilament
1
2
3
4
5

Слайд 59Fine-Tuning of the Response
Multistep pathways have two important benefits:
Amplifying the

signal (and thus the response)
Contributing to the specificity of the

Слайд 60Signal Amplification
Enzyme cascades amplify the cell’s response
At each step, the

Слайд 61The Specificity of Cell Signaling and Coordination of the Response
Different

kinds of cells have different collections of proteins
These different proteins

Слайд 62Fig. 11-17
Signaling
molecule
Receptor
Relay
molecules
Response 1
Cell A. Pathway leads
to a single response.
Response 2
Response

3
Cell B. Pathway branches,
leading to two responses.
Response 4
Response 5
Activation
or inhibition
Cell

Слайд 63Fig. 11-17a
Signaling
molecule
Receptor
Relay
molecules
Response 1
Cell A. Pathway leads
to a single response.
Cell B.