Chapter 11: Cell Communication What do you know about cell communication? 1.What is the difference...
-
Upload
darren-henry -
Category
Documents
-
view
232 -
download
0
Transcript of Chapter 11: Cell Communication What do you know about cell communication? 1.What is the difference...
Chapter 11: Cell CommunicationWhat do you know about cell communication?1. What is the difference between paracrine signaling & endocrine signaling?
- Paracrine – local signaling from 1 cell to another in close range- Endocrine – long-distance signaling involving hormones
(a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid.
(b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell.
Hormone travelsin bloodstreamto target cells
(c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells.
Local regulator diffuses through extracellular fluid
Secretingcell
Target cell
Secretoryvesicle
Electrical signalalong nerve celltriggers release ofneurotransmitter
Neurotransmitter diffuses across
synapse
Target cellis stimulated
Local signaling Long-distance signaling
Endocrine cellBloodvessel
Targetcell
Figure 11.3 Communication by direct contact between cells
Plasma membranes
(a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes.
(b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces.
Plasmodesmatabetween plant cells
Gap junctionsbetween animal cells
Chapter 11: Cell Communication1. What is the difference between paracrine signaling & endocrine signaling?2. What are the 3 stages of cell signaling?
- Reception – ligand (signal molecule) binding to a receptor
EXTRACELLULARFLUID
Receptor
Signal molecule
Plasma membraneCYTOPLASM
Reception Transduction1 2
Chapter 11: Cell Communication1. What is the difference between paracrine signaling & endocrine signaling?2. What are the 3 stages of cell signaling?
- Reception – ligand (signal molecule) binding to a receptor- Transduction – conversion of the received signal to a specific
cellular response
EXTRACELLULARFLUID
Receptor
Signal molecule
Plasma membraneCYTOPLASM
Reception Transduction1 2
Relay molecules in a signal transduction pathway
Chapter 11: Cell Communication1. What is the difference between paracrine signaling & endocrine signaling?2. What are the 3 stages of cell signaling?
- Reception – ligand (signal molecule) binding to a receptor- Transduction – conversion of the received signal to a specific
cellular response- Response – cell’s response to the signal
EXTRACELLULARFLUID
Receptor
Signal molecule
Relay molecules in a signal transduction pathway
Plasma membraneCYTOPLASM
Activationof cellularresponse
Reception Transduction Response1 2 3
Chapter 11: Cell Communication1. What is the difference between paracrine signaling & endocrine signaling?2. What are the 3 stages of cell signaling?3. What are the 4 types of receptors?
- Intracellular receptors…..aka steroid hormone receptors- G-protein-linked receptors- Tyrosine kinase receptors - Ligand-gated ion channels
-membrane-bound (integral proteins)
Hormone(testosterone)
EXTRACELLULARFLUID
Receptorprotein
Plasmamembrane
Hormone-receptorcomplex
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein
The non-polar steroid hormone testosterone passes through the plasma membrane.
1
Testosterone bindsto a receptor proteinin the cytoplasm,activating it.
2
The hormone-receptor complexenters the nucleusand binds to specific genes.
3
The bound proteinstimulates thetranscription ofthe gene into mRNA.
4
The mRNA istranslated into aspecific protein.
5
Fig. 11.6 Steroid hormone interacting with an intracellular receptor
Chapter 11: Cell Communication1. What is the difference between paracrine signaling & endocrine signaling?2. What are the 3 stages of cell signaling?3. What are the 4 types of receptors?
- Intracellular receptors…..aka steroid hormone receptors- G-protein-linked receptors
- Associated with a cytoplasmic G-protein- G-protein binds either GDP (inactive) or GTP (active)- Ligand binding
- Causes a change in receptor shape which- Attracts the inactive G-protein- GTP displaces GDP activating the G-protein- Activated G-protein can then activate other specific molecules
- G-proteins have GTPase activity to hydrolyze & inactivate G-protein
Figure 11.7 Exploring Membrane Receptors
Signal-binding site
G-PROTEIN-LINKED RECEPTORS
G-protein-linkedreceptor
Plasma Membrane
EnzymeG-protein(inactive)CYTOPLASM
Cellular response
Activatedenzyme
Activatedreceptor
Signal molecule Inactiveenzyme
Segment thatinteracts withG proteins
GDP
GDP
GTP
GTP
P i
GDP
Chapter 11: Cell Communication1. What is the difference between paracrine signaling & endocrine signaling?2. What are the 3 stages of cell signaling?3. What are the 4 types of receptors?
- Intracellular receptors…..aka steroid hormone receptors- G-protein-linked receptors- Tyrosine kinase receptors
- Kinase – enzyme that phosphorylates- Ligand binding
- Causes receptor to form a dimer- Cytoplasmic tails phosphorylate each other - ATP is hydrolyzed & terminal phosphate is added to tyrosine aa
- Activated receptors can then activate specific relay proteins
RECEPTOR TYROSINE KINASES
Signalmolecule
Signal-binding site
CYTOPLASM
Tyrosines
Signal molecule Helix in the
Membrane
Tyr
Tyr
Tyr
Tyr
Tyr
TyrTyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
DimerReceptor tyrosinekinase proteins(inactive monomers)
P
P
PP
P
PTyr
Tyr
Tyr
Tyr
Tyr
TyrP
P
P
P
P
PCellularresponse 1
Inactiverelay proteins
Activatedrelay proteins
Cellularresponse 2
Activated tyrosine-kinase regions(unphosphorylateddimer)
Fully activated receptortyrosine-kinase(phosphorylateddimer)
6 ATP 6 ADP
Chapter 11: Cell Communication1. What is the difference between paracrine signaling & endocrine signaling?2. What are the 3 stages of cell signaling?3. What are the 4 types of receptors?
- Intracellular receptors…..aka steroid hormone receptors- G-protein-linked receptors- Tyrosine kinase receptors- Ligand-gated ion channels
- Ligand binding- Causes a change in shape- Allows specific ions to move down concentration gradient
- e.g. neurotransmitters between neurons
Gate close
Cellularresponse
Gate open
Gate close
Ligand-gatedion channel receptor
Plasma Membrane
Signalmolecule(ligand)
GateClosed Ions
ION CHANNEL RECEPTORS
Chapter 11: Cell Communication1. What is the difference between paracrine signaling & endocrine signaling?2. What are the 3 stages of cell signaling?
- Reception – ligand (signal molecule) binding to a receptor- Transduction – conversion of the received signal to a specific
cellular response
EXTRACELLULARFLUID
Receptor
Signal molecule
Plasma membraneCYTOPLASM
Reception Transduction1 2
Relay molecules in a signal transduction pathway
Chapter 11: Cell Communication1. What is the difference between paracrine signaling & endocrine signaling?2. What are the 3 stages of cell signaling?
- Reception – ligand (signal molecule) binding to a receptor- Transduction – conversion of the received signal to a specific
cellular response- Often done by protein phosphorylations
- Protein kinases phosphorylate other relay molecules (kinases)- Inactivated by phosphatases that remove phosphate groups
Figure 11.8 A phosphorylation cascade (involves several protein kinases)
Signal molecule
Activeproteinkinase
1
Activeproteinkinase
2
Activeproteinkinase
3
Inactiveprotein kinase
1
Inactiveprotein kinase
2
Inactiveprotein kinase
3
Inactiveprotein
Activeprotein
Cellularresponse
Receptor
P
P
P
P
P
P
ATPADP
ADP
ADP
ATP
ATP
PP
PP
PP
Activated relaymolecule
A relay moleculeactivates protein kinase 1.1
Active protein kinase 1transfers a phosphate from ATPto an inactive molecule ofprotein kinase 2, thus activatingthis second kinase.
2
Active protein kinase 2then catalyzes the phos-phorylation (and activation) ofprotein kinase 3.
3
Finally, active proteinkinase 3 phosphorylates aprotein (pink) that brings about the cell’s response tothe signal.
4 Enzymes called proteinphosphatases (PP)catalyze the removal ofthe phosphate groupsfrom the proteins, making them inactiveand available for reuse.
5
i
i
i
Phosphorylation cascade
Chapter 11: Cell Communication1. What is the difference between paracrine signaling & endocrine signaling?2. What are the 3 stages of cell signaling?
- Reception – ligand (signal molecule) binding to a receptor- Transduction – conversion of the received signal to a specific
cellular response- Often done by protein phosphorylations- 2nd messengers
- cAMP – cyclic AMP – adenylyl cyclase converts ATP to cAMP
O–O O
O
N
O
O
O
O
P P P
P
P P
O
O
O
O
O
OH
CH2
NH2 NH2 NH2
N
N
N
N
N
N
N
N
N
N
NO
O
O
ATP
Ch2CH2
O
OH OH
P
O O
H2O
HOAdenylyl cyclase Phoshodiesterase
Pyrophosphate
Cyclic AMP AMPOH OH
O
i
Fig 11.10 cAMP as a second messenger in a G-protein-signaling pathway
First messenger(signal moleculesuch as epinephrine)
ATP
GTP
cAMP
Proteinkinase A
Cellular responses
G-protein-linkedreceptor
Adenylylcyclase
G protein
Second messenger
Chapter 11: Cell Communication1. What is the difference between paracrine signaling & endocrine signaling?2. What are the 3 stages of cell signaling?
- Reception – ligand (signal molecule) binding to a receptor- Transduction – conversion of the received signal to a specific
cellular response- Often done by protein phosphorylations- 2nd messengers
- cAMP – cyclic AMP – adenylyl cyclase converts ATP to cAMP- Ca+2 ions
- Released from ER- Muscle contractions- Cell division
Figure 11.11 Maintenance of calcium ion concentrations in an animal cell
EXTRACELLULARFLUID
Plasmamembrane
ATP
CYTOSOL
ATP Ca2+
pump
Ca2+
pump
Ca2+
pump
Endoplasmicreticulum (ER)
Nucleus
Mitochondrion
Key High [Ca2+] Low [Ca2+]
Figure 11.12 Calcium and IP3 in signaling pathways
IP3 quickly diffuses throughthe cytosol and binds to an IP3–gated calcium channel in the ERmembrane, causing it to open.
4
IP3
(second messenger)
DAG
3 DAG functions asa second messengerin other pathways.
Phospholipase C cleaves aplasma membrane phospholipidcalled PIP2 into DAG and IP3.
EXTRA-CELLULARFLUID
Signal molecule(first messenger)
G protein
G-protein-linkedreceptor
Endoplasmicreticulum (ER)
Phospholipase CPIP2
GTP
Ca2+
IP3-gatedcalcium channel
A signal molecule bindsto a receptor, leading toactivation of phospholipase C.
1 2
CYTOSOL
How does Ca+2 get released from the ER?- more 2nd messengers- IP3
- follow the numbers
Figure 11.12 Calcium and IP3 in signaling pathways
Calcium ions flow out ofthe ER (down their con-centration gradient), raisingthe Ca2+ level in the cytosol.
5
321
IP3 quickly diffuses throughthe cytosol and binds to an IP3–gated calcium channel in the ERmembrane, causing it to open.
4
Phospholipase C cleaves aplasma membrane phospholipidcalled PIP2 into DAG and IP3.
A signal molecule bindsto a receptor, leading toactivation of phospholipase C.
EXTRA-CELLULARFLUID
Signal molecule(first messenger)
G protein
G-protein-linkedreceptor
Endoplasmicreticulum (ER)
Phospholipase CPIP2
IP3
(second messenger)
DAG
GTP
Ca2+
(second messenger)
Ca2+
IP3-gatedcalcium channel
DAG functions as a second messenger In other pathways.
CYTOSOL
Figure 11.12 Calcium and IP3 in signaling pathways
2 3
IP3 quickly diffuses throughthe cytosol and binds to an IP3–gated calcium channel in the ERmembrane, causing it to open.
4 The calcium ionsactivate the nextprotein in one or moresignaling pathways.
6 Calcium ions flow out ofthe ER (down their con-centration gradient), raisingthe Ca2+ level in the cytosol.
5
DAG functions asa second messengerin other pathways.
Phospholipase C cleaves aplasma membrane phospholipidcalled PIP2 into DAG and IP3.
EXTRA-CELLULARFLUID
Signal molecule(first messenger)
G protein
G-protein-linkedreceptor
Variousproteinsactivated
Endoplasmicreticulum (ER)
Phospholipase CPIP2
IP3
(second messenger)
DAG
Cellularresponses
GTP
Ca2+
(second messenger)
Ca2+
IP3-gatedcalcium channel
A signal molecule bindsto a receptor, leading toactivation of phospholipase C.
1
CYTOSOL
Chapter 11: Cell Communication1. What is the difference between paracrine signaling & endocrine signaling?2. What are the 3 stages of cell signaling?
- Reception – ligand (signal molecule) binding to a receptor- Transduction – conversion of the received signal to a specific
cellular response- Often done by protein phosphorylations
- Protein kinases phosphorylate other relay molecules (kinases)- Inactivated by phosphatases
- 2nd messengers- cAMP – cyclic AMP – adenylyl cyclase converts ATP to cAMP- Ca+2 ions - IP3 - inositol triphosphate- DAG – diacyl glycerol
- Response – cell’s response to the signal3. What is meant by signal amplification?
- A single ligand can activate millions of molecules during a cell’s response
Figure 11.13 Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine
Glucose-1-phosphate(108 molecules)
Glycogen
Active glycogen phosphorylase (106)
Inactive glycogen phosphorylase
Active phosphorylase kinase (105)
Inactive phosphorylase kinase
Inactive protein kinase A
Active protein kinase A (104)
ATPCyclic AMP (104)
Active adenylyl cyclase (102)
Inactive adenylyl cyclase
Inactive G protein
Active G protein (102 molecules)
Binding of epinephrine to G-protein-linked receptor (1 molecule)
Transduction
Response
Reception
- Cytoplasmic signal amplification
Figure 11.14 Nuclear responses to a signal: the activation of a specific gene by a growth factor
Growth factor Reception
Transduction
Response
mRNANUCLEUS
Gene
P
Activetranscriptionfactor
Inactivetranscriptionfactor
DNA
Phosphorylationcascade
CYTOPLASM
Receptor- Nuclear signal amplification
Chapter 11: Cell Communication1. What is the difference between paracrine signaling & endocrine signaling?2. What are the 3 stages of cell signaling?3. What is meant my signal amplification?4. How can cells have different responses to the same signal?
- Different relay proteins- Cross-talk w/ diff. signals- Different receptor types
Response 1
Response 4 Response 5
Response 2 Response 3
Cell A. Pathway leads to a single response
Cell B. Pathway branches, leading to two responses
Cell C. Cross-talk occurs between two pathways
Cell D. Different receptorleads to a different response
Activationor inhibition
Receptor
Relaymolecules
Signalmolecule
Chapter 11: Cell Communication1. What is the difference between paracrine signaling & endocrine signaling?2. What are the 3 stages of cell signaling?3. What is meant my signal amplification?4. How can cells have different responses to the same signal?5. How do scaffolding proteins help cell communication?
- By binding several different molecules together for quicker process
Signalmolecule
Receptor
Scaffoldingprotein
Threedifferentproteinkinases
Plasmamembrane