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Chapter 11Cell Communication

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The Cellular “Internet” Within multicellular organisms, cells must

communicate with one another to coordinate their activities

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 are very similar in all organisms, even organisms as different as unicellular yeasts and multicellular mammals

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Communication Communication MethodsMethods Cell-to-cell contact Local signaling Long distance signaling

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Cell-to-Cell Cell-to-Cell CommunicationsCommunications Cell (gap) junctions must directly connect the

cytoplasm of adjacent cells; Protein channels connecting two adjoining cells

Animal cells use gap junctions to send signals Ex: cardiac cells for rhythmicity; Surface receptors can give/send information Ex: specific immune response

Plasma membranes

Plasmodesmatabetween plant cells

Gap junctionsbetween animal cells

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Cell-Cell Communication

Plasmodesmata between plant cells

Plant cells use plasmodesmata to send signals Cells must be in direct contact Gaps in the cell wall connecting the two

adjoining cells together

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Local Signaling Other types of signaling over a short

distance Cell-cell recognition

Membrane bound cell surface molecules Glycoproteins Glyolipids

Local regulators Growth factors Only work over a short distance

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Long-Distance Signaling Nervous System in Animals

Electrical signals through neurons

Endocrine System in Animals Uses hormones to transmit messages over

long distances

Plants also use hormones Some transported through vascular system Others are released into the air

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Local/Long-Distance Signaling

Messenger molecules can also be secreted by the signaling cell Paracrine signaling:

One cell secretes (releases) molecules that act on nearby “target” cells Example: growth factors

Synaptic Signaling: Nerve cells release chemical messengers (neurotransmitters) that

stimulate the target cell

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Long-Distance Signaling

Endocrine (hormone) signaling Specialized cells

release hormone molecules, which travel (usually by diffusion through cells or through the circulatory system) to target cells elsewhere in the organism

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The Three Stages of Cell Signaling

There are 3 stages at the “receiving end” of a cellular conversation:

1. Reception2. Transduction3. Response

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Reception1

EXTRACELLULARFLUID

Receptor

Signalingmolecule

Plasma membrane

CYTOPLASM

1

Step One - Reception

Signaling molecule (ligand)

binds to the receptor protein

The receptor and signaling molecules fit together (lock and key model, induced fit model, just like enzymes!)

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Step 1: Reception

The target cell “detects” that there is a signal molecule coming from outside the cell The signal is detected when it binds to a protein on the cell’s

surface or inside the cell The signal molecule “searches out” specific receptor proteins

The signal molecule is a ligand It is a molecule that specifically binds to another one (think enzymes!)

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Step Two - Transduction

Reception1

EXTRACELLULARFLUID

Receptor

Signalingmolecule

Plasma membrane

CYTOPLASM

1

Relay molecules in a signal transduction pathway

Transduction2

The signal is converted into a form that can produce a cellular response

2nd Messenger!

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Step 2: Transduction This stage converts the signal into a

form that can bring about a specific cellular response One signal-activated receptor activates

another protein, which activates another molecule, etc., etc.

These act as relay molecules Often the message is transferred using

protein kinases, which transfer phosphate groups from ATP molecules to proteins

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Signal molecule

Activeproteinkinase

1

Activeproteinkinase

2

Activeproteinkinase

3

Inactiveprotein kinase

1

Inactiveprotein kinase

2

Inactiveprotein kinase

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

Step 2 – Transduction (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

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EXTRACELLULARFLUID

Plasma membrane

CYTOPLASM

Receptor

Signalingmolecule

Relay molecules in a signal transduction pathway

Activationof cellularresponse

Reception Transduction Response1 2 3

Step Three - Response

The transduced signal triggers a cellular response

Can be catalysis, activation of a gene, triggering apoptosis, almost anything!

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Step 3: Response

The signal that was passed through the signal transduction pathway triggers a specific cellular response Examples: enzyme

action, cytoskeleton rearrangement, activation of genes, etc., etc.

Diagram example: transcription of mRNA

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The Specificity of Cell Signaling

The particular proteins that a cell possesses determine which signal molecules it will respond to and how it will respond to them

Liver cells and heart cells, for example, do not respond in the same way to epinephrine because they have different collections of proteins

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There are three main types of plasma membrane receptors:G-protein-linkedTyrosine kinasesIon channel

Types of ReceptorsTypes of Receptors

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G-protein-linked receptorsG-protein-linked receptors Very common Results in a single pathway response

G-protein-linkedReceptor

Plasma Membrane

EnzymeG-protein(inactive)CYTOPLASM

Cellular response

Activatedenzyme

ActivatedReceptor

Signal molecule Inactivateenzyme

GDP

GDP

GTP

GTP

P i

GDP

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Receptor tyrosine kinasesReceptor tyrosine kinases Multiple pathway response

Signalmolecule

Signal-binding site

CYTOPLASM

Tyrosines

Signal moleculeHelix in the

Membrane

Tyr

TyrTyr

TyrTyr

TyrTyr

TyrTyr

TyrTyr

Tyr

TyrTyrTyr

TyrTyr

Tyr Tyr

TyrTyr

TyrTyr

Tyr

Tyr

TyrTyr

TyrTyr

Tyr

DimerReceptor tyrosinekinase proteins(inactive monomers)

PPP

PP

P Tyr

TyrTyr

TyrTyr

TyrP

PP

PP

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

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Signalingmolecule(ligand)

Gateclosed Ions

Ligand-gatedion channel receptor

Plasmamembrane

Gate open

Cellularresponse

Gate closed

1

2

3

Ion Channel Receptors Very important in

the nervous system

When ligand binds, channel can open or close. depolarization Triggered by

neurotransmitters

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Hormone(testosterone)

EXTRACELLULARFLUID

Receptorprotein

DNA

mRNA

NUCLEUS

CYTOPLASM

Plasmamembrane

Hormone-receptorcomplex

New protein

Figure 11.6

*Intracellular Receptors*Intracellular Receptors Target protein is INSIDE the cell Must be hydrophobic molecule

1 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

Why can the signal molecule meet its target INSIDE the cell?

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First messengerFig. 11-11

G protein

Adenylylcyclase

GTP

ATP

cAMPSecondmessenger

Proteinkinase A

G protein-coupledreceptor

Cellular responses

Transduction in a G-protein pathway

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Response Many possible

outcomes This example

shows a transcription response

Growth factor

Receptor

Phosphorylationcascade

Reception

Transduction

Activetranscriptionfactor Response

P

Inactivetranscriptionfactor

CYTOPLASM

DNA

NUCLEUSmRNA

Gene

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The signal can also trigger an activator or inhibitor

The signal can also trigger multiple receptors and different responses Response 4 Response 5

Activationor inhibition

Cell C. Cross-talk occursbetween two pathways.

Cell D. Different receptorleads to a different response.

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Yeast Sexual ReproductionYeast Sexual Reproduction

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 a cells.

2

3

factorYeast cell,mating type a

Yeast cell,mating type

a/

a

a

Yeast cells identify their mates by cell

signaling.

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Evolutionary Significance Unicellular and multicellular cell

communication have similarities Yeast cells signal for sexual

reproduction through signal transduction process.

Bacteria secrete molecules to sense density of own population. Quorum Sensing (survival purpose)

TEDED on Quorum Sensing