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Chapter 11: Cell Communication1. 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


- Reception – ligand (signal molecule) binding to a receptor- Transduction – conversion of the received signal to a specific

cellular response

EXTRACELLULARFLUID

Receptor

Signal molecule



Relay molecules in a signal transduction pathway



cellular response- Response – cell’s response to the signal

EXTRACELLULARFLUID

Receptor

Signal molecule



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


- 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

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


- 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 because…- 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


- 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



cellular response

EXTRACELLULARFLUID

Receptor

Signal molecule






cellular response- Often done by protein phosphorylations

- Protein kinases phosphorylate other relay molecules (kinases)- Inactivated by phosphatases

Figure 11.8 A phosphorylation cascade (involves several protein kinases)

Signal molecule

Activeproteinkinase

1

Activeproteinkinase

2

Activeproteinkinase

3

Inactiveprotein kinase

1


2


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



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


Adenylylcyclase

G protein

Second messenger



cellular response- Often done by protein phosphorylations- 2nd messengers

- cAMP – cyclic AMP – adenylyl cyclase converts ATP to cAMP- Ca+2 ions

- Released from ER

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



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


Calcium ions flow out ofthe ER (down their con-centration gradient), raisingthe Ca2+ level in the cytosol.

5

321


4



EXTRA-CELLULARFLUID


G protein



Phospholipase CPIP2

IP3

(second messenger)

DAG

GTP

Ca2+

(second messenger)

Ca2+


DAG functions as a second messenger In other pathways.

CYTOSOL


2 3


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.


EXTRA-CELLULARFLUID


G protein


Variousproteinsactivated


Phospholipase CPIP2

IP3

(second messenger)

DAG

Cellularresponses

GTP

Ca2+

(second messenger)

Ca2+



1

CYTOSOL



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

- 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

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