chapter 6a communication, integration, and homeostasis
TRANSCRIPT
About this Chapter
• Cell-to-cell communication• Signal pathways• Novel signal molecules• Modulation of signal pathways• Control pathways• Response loops• Feedback loops
Cell-to-Cell Communication: Overview
• Physiological signals• Electrical signals• Changes in the membrane potential of a cell
• Chemical signals• Secreted by cells into ECF• Responsible for most communication within the
body
• Target cells, or targets, receive signals• Four basic methods of communication
Figure 6-1a
Cell-to-Cell Communication: Methods
• Direct contact and local cell-to-cell communication
• Gap junctions• Transfer both
chemical and electrical signals
• Form direct cytoplasmic connections between adjacent cells.
• Protein connexins form a connexon channel
Cell-to-Cell Communication: Methods
• CAMs, cell adhesion molecules, transfer signals in both directions
• Common in Immune system
• Contact-dependent signals require interaction between membrane molecules on two cells.
Figure 6-1b
Cell-to-Cell Communication: Methods
• Direct contact and local cell-to-cell communication
• Autocrine signals act on the same cell that secreted them. Paracrine signals are secreted by one cell and diffuse to adjacent cells.
Figure 6-1c(c) Autocrine signals and paracrine signals
Receptor
Cell-to-Cell Communication: Methods
• Paracrine and autocrine are chemical signals
• Hormones are secreted by endocrine glands or cells into the blood. Only target cells with receptors for the hormone will respond to the signal.
Figure 6-2a
(a) Hormones
Endocrinecell
Cellwithoutreceptor
Cellwith
receptor
No response
Targetcell
Response
Blood
Cell-to-Cell Communication: Methods
• Long distance cell-to-cell communication• Neurotransmitters are chemicals secreted by
neurons that diffuse across a small gap to the target cell. Neurons use electrical signals as well.
• Neurotransmitters have a rapid effect
Figure 6-2b
(b) Neurotransmitters
Neuron
Electricalsignal Target
cell
Cell-to-Cell Communication: Methods
• Neurohormones are chemicals released by neurons into the blood for action at distant targets.
Figure 6-2c
Cellwithoutreceptor
Cellwith
receptor
No response(c) Neurohormones
Neuron
Response
Blood
Cell-to-Cell Communication: Methods
• Cytokines may act as both local and long-distance signals
• All nucleated cells synthesize and secrete cytokines in response to stimuli
• In development and differentiation, cytokines usually function as autocrine or paracrine signals
• In stress and inflammation, some cytokines may act on relatively distant targets
Signal Pathways: Overview
Figure 6-3
Receptorprotein
Intracellularsignal
molecules
Signalmolecule
Target proteins
Response
binds to
activates
alters
create
Signal Pathways: Receptor locations
• Target cell receptors• Lipophilic vs lipophobic
Figure 6-4 (1 of 2)
Slower responsesrelated to changes
in gene activity
Receptor in cytosol
Receptorin nucleus
Lipophilic signalmolecules
Lipophobic orlipophilic signalmolecules
Signal Pathways: Receptor locations
Figure 6-4 (2 of 2)
Lipophobic signal molecule
Receptor
Ligand-receptor complex
Rapid cellularresponses
Extracellular fluid
Intracellular fluid
Cell membrane
Signal Pathways: Membrane Receptors
• Four categories of membrane receptors
Figure 6-5
Cellmembrane
ECF
ICFG protein
ReceptorChannel
Extracellularsignal
molecules
IntegrinReceptor
Enzyme
Anchorprotein
Cytoskeleton
Receptor-channel
Receptor-enzyme Integrin receptorG protein-coupled receptor
Signal molecule
Receptor
Intracellularsignal molecules
Signal Transduction
Figure 6-6
Radio
Radio waves
Receptor
Transducer
Amplifier
Response
External signal
Sound waves
Signal transduction converts one form of signal into a different form.
Signal Pathways: Signal Amplification
• Transducers convert extracellular signals into intracellular messages which create a response
Figure 6-7
Extracellularfluid
Intracellularfluid
Cellmembrane
Receptor-ligand complex activates an
amplifier enzyme (AE).Signal molecule
Receptor
Intracellularsignal moleculesTarget proteins
Signal Pathway: Biological Signal Transduction
• Biological signal transduction converts chemical signals into cellular responses
Figure 6-8
alter
Signalmolecule
Membrane receptor
Signal transduction by proteins
Amplifier enzymes
Second messengermolecules
Protein kinases Increaseintracellular Ca2+
Phosphorylatedproteins
Calcium-bindingproteins
Extracellularfluid
Intracellularfluid
Cell response
initiates
binds to
Ionchannel
Signal molecule
Receptor
Intracellularsignal moleculesTarget proteins
Response
Signal Pathway: Signal Transduction
• Steps of signal transduction pathway form a cascade
Figure 6-9
Inactive A
Inactive B
Inactive C
Substrate
Active A
Active B
Active C
Product
Initialstimulus
Signal Pathway: Receptor Enzymes
• Tyrosine kinase, an example of receptor-enzyme
Figure 6-10
+ Protein
Active binding site
+ ADP
ECF
ICF
Signal molecule binds to surface receptor
Phosphorylatedprotein
Tyrosine kinase oncytoplasmic side
Cellmembrane
activates
Protein
Signal molecule
Receptor
Intracellularsignal molecules
ATP
Signal Pathway: GPCR
• Membrane-spanning proteins• Cytoplasmic tail linked to G protein, a three-
part transducer molecule • When G proteins are activated, they• Open ion channels in the membrane• Alter enzyme activity on the cytoplasmic side of
the membrane
GPCR: Adenylyl Cyclase-cAMP
Figure 6-11
1
One signalmolecule
Adenylylcyclase
ATP
cAMP
G protein
Proteinkinase A
Phosphorylatedprotein
Cellresponse
Signal molecule binds toG protein-linked receptor,which activates the G protein.
Protein kinase A phosphorylatesother proteins, leading ultimatelyto a cellular response.
G protein turns on adenylylcyclase, an amplifier enzyme.
Adenylyl cyclase convertsATP to cyclic AMP.
cAMP activates proteinkinase A.
23
4
5
1
2
3
4
5
GPCR: Adenylyl Cyclase-cAMP
Figure 6-11, step 1
1
One signalmolecule
G protein
Signal molecule binds toG protein-linked receptor,which activates the G protein.
1
GPCR: Adenylyl Cyclase-cAMP
Figure 6-11, steps 1–2
1
One signalmolecule
Adenylylcyclase
G protein
Signal molecule binds toG protein-linked receptor,which activates the G protein.
G protein turns on adenylylcyclase, an amplifier enzyme.2
1
2
GPCR: Adenylyl Cyclase-cAMP
Figure 6-11, steps 1–3
1
One signalmolecule
Adenylylcyclase
ATP
cAMP
G protein
Signal molecule binds toG protein-linked receptor,which activates the G protein.
G protein turns on adenylylcyclase, an amplifier enzyme.
Adenylyl cyclase convertsATP to cyclic AMP.
23
1
2
3
GPCR: Adenylyl Cyclase-cAMP
Figure 6-11, steps 1–4
1
One signalmolecule
Adenylylcyclase
ATP
cAMP
G protein
Proteinkinase A
Signal molecule binds toG protein-linked receptor,which activates the G protein.
G protein turns on adenylylcyclase, an amplifier enzyme.
Adenylyl cyclase convertsATP to cyclic AMP.
cAMP activates proteinkinase A.
23
4
1
2
3
4
GPCR: Adenylyl Cyclase-cAMP
Figure 6-11, steps 1–5
1
One signalmolecule
Adenylylcyclase
ATP
cAMP
G protein
Proteinkinase A
Phosphorylatedprotein
Cellresponse
Signal molecule binds toG protein-linked receptor,which activates the G protein.
Protein kinase A phosphorylatesother proteins, leading ultimatelyto a cellular response.
G protein turns on adenylylcyclase, an amplifier enzyme.
Adenylyl cyclase convertsATP to cyclic AMP.
cAMP activates proteinkinase A.
23
4
5
1
2
3
4
5
GPCR: The Phospholipase C System
Figure 6-12
1
Membrane phospholipid
Protein + Pi
Cellmembrane
Extracellularfluid
Intracellularfluid
DAG
Phosphorylatedprotein
PL-CDAGPK-CIP3
ER
=====
phospholipase Cdiacylglycerolprotein kinase Cinositol trisphosphateendoplasmic reticulum
ER
ReceptorG protein
Cellularresponse
Signal molecule
Signal moleculeactivates receptorand associatedG protein.
G protein activatesphospholipase C (PL-C), an amplifier enzyme.
PL-C converts membranephospholipids intodiacylglycerol (DAG) whichremains in the membrane,and IP3, which diffusesinto the cytoplasm.
DAG activates proteinkinase C (PK-C), whichphosphorylates proteins.
IP3 causes releaseof Ca2+ fromorganelles, creatinga Ca2+ signal.
KEY
PL-C
IP3
PK-C
Ca2+ stores Ca2+
2 34
5
1 2 3 4 5
GPCR: The Phospholipase C System
Figure 6-12, step 1
1
Cellmembrane
Extracellularfluid
Intracellularfluid
PL-CDAGPK-CIP3
ER
=====
phospholipase Cdiacylglycerolprotein kinase Cinositol trisphosphateendoplasmic reticulum
ReceptorG protein
Signal molecule
Signal moleculeactivates receptorand associatedG protein.
KEY
1
GPCR: The Phospholipase C System
Figure 6-12, steps 1–2
1
Cellmembrane
Extracellularfluid
Intracellularfluid
PL-CDAGPK-CIP3
ER
=====
phospholipase Cdiacylglycerolprotein kinase Cinositol trisphosphateendoplasmic reticulum
ReceptorG protein
Signal molecule
Signal moleculeactivates receptorand associatedG protein.
G protein activatesphospholipase C (PL-C), an amplifier enzyme.
KEY
PL-C2
1 2
GPCR: The Phospholipase C System
Figure 6-12, steps 1–3
1
Membrane phospholipidCell
membrane
Extracellularfluid
Intracellularfluid
DAG
PL-CDAGPK-CIP3
ER
=====
phospholipase Cdiacylglycerolprotein kinase Cinositol trisphosphateendoplasmic reticulum
ReceptorG protein
Signal molecule
Signal moleculeactivates receptorand associatedG protein.
G protein activatesphospholipase C (PL-C), an amplifier enzyme.
PL-C converts membranephospholipids intodiacylglycerol (DAG) whichremains in the membrane,and IP3, which diffusesinto the cytoplasm.
KEY
PL-C
IP3
2 3
1 2 3
GPCR: The Phospholipase C System
Figure 6-12, steps 1–4
1
Membrane phospholipid
Protein + Pi
Cellmembrane
Extracellularfluid
Intracellularfluid
DAG
Phosphorylatedprotein
PL-CDAGPK-CIP3
ER
=====
phospholipase Cdiacylglycerolprotein kinase Cinositol trisphosphateendoplasmic reticulum
ReceptorG protein
Cellularresponse
Signal molecule
Signal moleculeactivates receptorand associatedG protein.
G protein activatesphospholipase C (PL-C), an amplifier enzyme.
PL-C converts membranephospholipids intodiacylglycerol (DAG) whichremains in the membrane,and IP3, which diffusesinto the cytoplasm.
DAG activates proteinkinase C (PK-C), whichphosphorylates proteins.
KEY
PL-C
IP3
PK-C
2 34
1 2 3 4
GPCR: The Phospholipase C System
Figure 6-12, steps 1–5
1
Membrane phospholipid
Protein + Pi
Cellmembrane
Extracellularfluid
Intracellularfluid
DAG
Phosphorylatedprotein
PL-CDAGPK-CIP3
ER
=====
phospholipase Cdiacylglycerolprotein kinase Cinositol trisphosphateendoplasmic reticulum
ER
ReceptorG protein
Cellularresponse
Signal molecule
Signal moleculeactivates receptorand associatedG protein.
G protein activatesphospholipase C (PL-C), an amplifier enzyme.
PL-C converts membranephospholipids intodiacylglycerol (DAG) whichremains in the membrane,and IP3, which diffusesinto the cytoplasm.
DAG activates proteinkinase C (PK-C), whichphosphorylates proteins.
IP3 causes releaseof Ca2+ fromorganelles, creatinga Ca2+ signal.
KEY
PL-C
IP3
PK-C
Ca2+ stores Ca2+
2 34
5
1 2 3 4 5
Signal Pathway: Receptor-Channel
• Some second messengers create electrical signals
Figure 6-13
1
Receptor-channels open orclose in response to signalmolecule binding.
Some channels are directlylinked to G proteins.
Other ligand-gated channelsrespond to intracellularsecond messengers.
Extracellularsignal
molecules
Ions
Ionchannel
G protein
Change in membranepermeability to
Na+, K+, Cl–
Creates electricalsignal
Voltage-sensitiveprotein
Cellularresponse
G protein-coupledreceptor
Intracellularsignal molecules
2
3
2
3
1
Signal Pathway: Receptor-Channel
Figure 6-13, step 1
1
Receptor-channels open orclose in response to signalmolecule binding.
Extracellularsignal
molecules
Ions
Ionchannel
1
Signal Pathway: Receptor-Channel
Figure 6-13, steps 1–2
1
Receptor-channels open orclose in response to signalmolecule binding.
Some channels are directlylinked to G proteins.
Extracellularsignal
molecules
Ions
Ionchannel
G protein
G protein-coupledreceptor
2
2
1
Signal Pathway: Receptor-Channel
Figure 6-13, steps 1–3
1
Receptor-channels open orclose in response to signalmolecule binding.
Some channels are directlylinked to G proteins.
Other ligand-gated channelsrespond to intracellularsecond messengers.
Extracellularsignal
molecules
Ions
Ionchannel
G protein
G protein-coupledreceptor
Intracellularsignal molecules
2
3
2
3
1
Signal Pathway: Receptor-Channel
Figure 6-13
1
Receptor-channels open orclose in response to signalmolecule binding.
Some channels are directlylinked to G proteins.
Other ligand-gated channelsrespond to intracellularsecond messengers.
Extracellularsignal
molecules
Ions
Ionchannel
G protein
Change in membranepermeability to
Na+, K+, Cl–
Creates electricalsignal
Voltage-sensitiveprotein
Cellularresponse
G protein-coupledreceptor
Intracellularsignal molecules
2
3
2
3
1
Signal Pathway: Signal Transduction
• Summary map of signal transduction systems
Figure 6-14
Ions
Gated ion channel
alters
alter
creates
produces
activate
phosphorylate
will be a change in
phosphorylates
Extracellularfluid
Intracellularfluid
Cell membrane
Protein kinases
Altered proteins
Change in ionconcentration
Electrical signal
Ions moveinto or out
of cell
Motorproteins
Enzymeactivity
Membranereceptors and transporters
Gene activityand proteinsynthesis
Activates orinhibits
amplifier enzyme
Second messengermolecules
Triggersrelease ofCa2+ fromorganelles
Signalmolecule
ActivatesG protein
Activatestyrosinekinase
Alterscytoskeleton
Cellular responses
bindto
Membranereceptor