chap.11 cellcommunication

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

PowerPoint Lectures for Biology, Seventh Edition

Neil Campbell and Jane Reece

Lectures by Chris Romero

Chapter 11Chapter 11

Cell Communication


• Overview: The Cellular Internet

• Cell-to-cell communication

– Is absolutely essential for multicellular organisms


• Biologists

– Have discovered some universal mechanisms of cellular regulation

Figure 11.1


Evolution of Cell Signaling

• Yeast cells

– Identify their mates by cell signaling

factorReceptor

Exchange of mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type.

1

Mating. Binding of the factors to receptors induces changes in the cells that lead to their fusion.

New a/ cell. The nucleus of the fused cell includes all the genes from the a and α cells.

2

3

factorYeast cell,mating type a

Yeast cell,mating type

a/

a

a

Figure 11.2


• Concept 11.1: External signals are converted into responses within the cell


• Signal transduction pathways

– Convert signals on a cell’s surface into cellular responses

– Are similar in microbes and mammals, suggesting an early origin


Local and Long-Distance Signaling

• Cells in a multicellular organism

– Communicate via chemical messengers


• Animal and plant cells

– Have cell junctions that directly connect the cytoplasm of adjacent cells

Plasma membranes

Plasmodesmatabetween plant cells

Gap junctionsbetween animal cells

Figure 11.3 (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes.


Figure 11.3 (b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces.

• In local signaling, animal cells

– May communicate via direct contact


• In other cases, animal cells

– Communicate using local regulators

(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.

Local regulator diffuses through extracellular fluid

Target cell

Secretoryvesicle

Electrical signalalong nerve celltriggers release ofneurotransmitter

Neurotransmitter diffuses across

synapse

Target cellis stimulated

Local signaling

Figure 11.4 A B


• In long-distance signaling

– Both plants and animals use hormones

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.

Long-distance signaling

Bloodvessel

Targetcell

Endocrine cell

Figure 11.4 C


The 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


EXTRACELLULARFLUID

Receptor

Signal molecule

Relay molecules in a signal transduction pathway

Plasma membraneCYTOPLASM

Activationof cellularresponse

Figure 11.5

• Overview of cell signaling

Reception1 Transduction2 Response3


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


• The binding between signal molecule (ligand)

– And receptor is highly specific

• A conformational change in a receptor

– Is often the initial transduction of the signal


Intracellular Receptors

• Intracellular receptors

– Are cytoplasmic or nuclear proteins


• Signal molecules that are small or hydrophobic

– And can readily cross the plasma membrane use these receptors


Hormone(testosterone)

EXTRACELLULARFLUID

Receptorprotein

DNA

mRNA

NUCLEUS

CYTOPLASM

Plasmamembrane

Hormone-receptorcomplex

New protein

Figure 11.6

• Steroid hormones

– Bind to intracellular receptors1 The steroid hormone testosterone passes through the plasma membrane.

The bound proteinstimulates thetranscription ofthe gene into mRNA.

4

The mRNA istranslated into aspecific protein.

5

Testosterone bindsto a receptor proteinin the cytoplasm,activating it.

2

The hormone-receptor complexenters the nucleusand binds to specific genes.

3


Receptors in the Plasma Membrane

• There are three main types of membrane receptors

– G-protein-linked

– Tyrosine kinases

– Ion channel


• G-protein-linked receptors

G-protein-linkedReceptor

Plasma Membrane

EnzymeG-protein(inactive)CYTOPLASM

Cellular response

Activatedenzyme

ActivatedReceptor

Signal molecule Inctivateenzyme

Segment thatinteracts withG proteins

GDP

GDP

GTP

GTP

P i

Signal-binding site

Figure 11.7

GDP


• Receptor tyrosine kinasesSignalmolecule

Signal-binding sitea

CYTOPLASM

Tyrosines

Signal moleculeHelix 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

P Tyr

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

Figure 11.7


• Ion channel receptors

Cellularresponse

Gate open

Gate close

Ligand-gatedion channel receptor

Plasma Membrane

Signalmolecule(ligand)

Figure 11.7

Gate closed Ions


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

• Multistep pathways

– Can amplify a signal

– Provide more opportunities for coordination and regulation


Signal Transduction Pathways

• At each step in a pathway

– The signal is transduced into a different form, commonly a conformational change in a protein


Protein Phosphorylation and Dephosphorylation

• Many signal pathways

– Include phosphorylation cascades


• In this process

– A series of protein kinases add a phosphate to the next one in line, activating it

– Phosphatase enzymes then remove the phosphates


Signal molecule

Activeproteinkinase

1

Activeproteinkinase

2

Activeproteinkinase

3

Inactiveprotein kinase

1


2


3

Inactiveprotein

Activeprotein

Cellularresponse

Receptor

P

P

P

ATPADP

ADP

ADP

ATP

ATP

PP

PP

PP

Activated relaymolecule

i

Phosphorylation cascade

P

P

i

i

P

• A phosphorylation cascade

Figure 11.8

A relay moleculeactivates protein kinase 1.

1

2 Active protein kinase 1transfers a phosphate from ATPto an inactive molecule ofprotein kinase 2, thus activatingthis second kinase.

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


Small Molecules and Ions as Second Messengers

• Second messengers

– Are small, nonprotein, water-soluble molecules or ions


Cyclic AMP

• Cyclic AMP (cAMP)

– Is made from ATP

Figure 11.9

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


• Many G-proteins

– Trigger the formation of cAMP, which then acts as a second messenger in cellular pathways

ATP

GTP

cAMP

Proteinkinase A

Cellular responses

G-protein-linkedreceptor

AdenylylcyclaseG protein

First messenger(signal moleculesuch as epinephrine)

Figure 11.10


Calcium ions and Inositol Triphosphate (IP3)

• Calcium, when released into the cytosol of a cell

– Acts as a second messenger in many different pathways


• Calcium is an important second messenger

– Because cells are able to regulate its concentration in the cytosol

EXTRACELLULARFLUID

Plasmamembrane

ATP

CYTOSOL

ATP Ca2+

pump

Ca2+

pump

Ca2+

pump

Endoplasmicreticulum (ER)

Nucleus

Mitochondrion

Key High [Ca2+] Low [Ca2+]Figure 11.11


• Other second messengers such as inositol triphosphate and diacylglycerol

– Can trigger an increase in calcium in the cytosol


Figure 11.12

321

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.

A signal molecule bindsto a receptor, leading toactivation of phospholipase C.

EXTRA-CELLULARFLUID

Signal molecule(first messenger)

G protein

G-protein-linkedreceptor

Variousproteinsactivated

Endoplasmicreticulum (ER)

Phospholipase CPIP2

IP3

(second messenger)

DAG

Cellularresponse

GTP

Ca2+

(second messenger)

Ca2+

IP3-gatedcalcium channel


• Concept 11.4: Response: Cell signaling leads to regulation of cytoplasmic activities or transcription


Cytoplasmic and Nuclear Responses

• In the cytoplasm

– Signaling pathways regulate a variety of cellular activities


• Cytoplasmic response to a signal

Figure 11.13Glucose-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


• Other pathways

– Regulate genes by activating transcription factors that turn genes on or off

Reception

Transduction

Response

mRNANUCLEUS

Gene

P

Activetranscriptionfactor

Inactivetranscriptionfactor

DNA

Phosphorylationcascade

CYTOPLASM

Receptor

Growth factor

Figure 11.14


Fine-Tuning of the Response

• Signal pathways with multiple steps

– Can amplify the signal and contribute to the specificity of the response


Signal Amplification

• Each protein in a signaling pathway

– Amplifies the signal by activating multiple copies of the next component in the pathway


The Specificity of Cell Signaling

• The different combinations of proteins in a cell

– Give the cell great specificity in both the signals it detects and the responses it carries out


• Pathway branching and “cross-talk”

– Further help the cell coordinate incoming signals

Response 1

Response 4 Response 5

Response

2

Response

3

Signalmolecule

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

Figure 11.15


Signaling Efficiency: Scaffolding Proteins and Signaling Complexes

• Scaffolding proteins

– Can increase the signal transduction efficiency

Signalmolecule

Receptor

Scaffoldingprotein

Threedifferentproteinkinases

Plasmamembrane

Figure 11.16


Termination of the Signal

• Signal response is terminated quickly

– By the reversal of ligand binding

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