cell communication chapter 11 local regulators – in the vicinity a.paracrine signaling – nearby...

Cell Communication

Chapter 11Local regulators – in the vicinitya.Paracrine signaling – nearbyCells are acted on by signalingCell (ie. Growth factor)b. Synaptic signaling-neurotrans-mitters cross the synapse (gap)Between nerve cell and target

Long Distance Signaling

• Hormones–Endocrine signaling–Plant growth regulators

Figure 11.4 Plasma membranes

Gap junctionsbetween animal cells

Plasmodesmatabetween plant cells

(a) Cell junctions

(b) Cell-cell recognition

Figure 11.5

Local signaling Long-distance signaling

Target cell

Secretingcell

Secretoryvesicle

Local regulatordiffuses throughextracellular fluid.

(a) Paracrine signaling (b) Synaptic signaling

Electrical signalalong nerve celltriggers release ofneurotransmitter.

Neurotransmitter diffuses across synapse.

Target cellis stimulated.

Endocrine cell Bloodvessel

Hormone travelsin bloodstream.

Target cellspecificallybinds hormone.

(c) Endocrine (hormonal) signaling

The Three Stages of Cell Signaling: A Preview

–Reception–Transduction–Response

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Receptors in the Plasma Membrane

• There are three main types of membrane receptors

–G protein-coupled receptors–Receptor tyrosine kinases–Ion channel receptors

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ligand-gated ion channel receptor • acts as a gate when the receptor

changes shape• signal molecule binds as a ligand to

the receptor• the gate allows specific ions, such as

Na+ or Ca2+, through a channel in the receptor

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Figure 11.7d

Signalingmolecule (ligand)

21 3

Gate closed Ions

Ligand-gatedion channel receptor

Plasmamembrane

Gate open

Cellularresponse

Gate closed

G-protein-coupled receptor (GPCRs• works with the help of a G protein• The G protein acts as an on/off switch

• If GDP is bound to the G protein, the G protein is inactive

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Figure 11.7b

G protein-coupledreceptor

21

3 4

Plasmamembrane

G protein(inactive)

CYTOPLASM Enzyme

Activatedreceptor

Signalingmolecule

Inactiveenzyme

Activatedenzyme

Cellular response

GDPGTP

GDPGTP

GTP

P i

GDP

GDP

• Receptor tyrosine kinases (RTKs)• membrane receptors that attach

phosphates to tyrosines• can trigger multiple signal

transduction pathways at once• Abnormal functioning of RTKs is

associated with many types of cancers

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Figure 11.7c

Signalingmolecule (ligand)

21

3 4

Ligand-binding site

helix in themembrane

Tyrosines

CYTOPLASM Receptor tyrosinekinase proteins(inactive monomers)

Signalingmolecule

Dimer

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

P

P

P

P

P

P

P

P

P

P

P

P

Activated tyrosinekinase regions(unphosphorylateddimer)

Fully activatedreceptor tyrosinekinase(phosphorylateddimer)

Activated relayproteins

Cellularresponse 1

Cellularresponse 2

Inactiverelay proteins

6 ATP 6 ADP

Intracellular Receptors

• found in the cytosol or nucleus of target cells• Small or hydrophobic chemical messengers

can activate receptors• Examples of hydrophobic messengers are the

steroid and thyroid hormones of animals• An activated hormone-receptor complex can

act as a transcription factor, turning on specific genes

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• A ligand-gated ion channel receptor acts as a gate when the receptor changes shape

• When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor

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Figure 11.7d

Signalingmolecule (ligand)

21 3

Gate closed Ions

Ligand-gatedion channel receptor

Plasmamembrane

Gate open

Cellularresponse

Gate closed

Intracellular Receptors

• found in the cytosol or nucleus of target cells• Small or hydrophobic chemical messengers

can readily cross the membrane and activate receptors

• Examples of hydrophobic messengers are the steroid and thyroid hormones of animals

• An activated hormone-receptor complex can act as a transcription factor, turning on specific genes

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Figure 11.9-5Hormone(testosterone)

Receptorprotein

Plasmamembrane

EXTRACELLULARFLUID

Hormone-receptorcomplex

DNA

mRNA

NUCLEUS

CYTOPLASM

New protein

Signal Transduction Pathways

• mostly proteins• Produces a domino affect• At each step, the signal is transduced

into a different form, usually a shape change in a protein

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Protein Phosphorylation and Dephosphorylation

• Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation

• Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation

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Receptor

Signaling molecule

Activated relaymolecule

Phosphorylation cascade

Inactiveprotein kinase

1 Activeprotein kinase

1

Activeprotein kinase

2

Activeprotein kinase

3

Inactiveprotein kinase

2

Inactiveprotein kinase

3

Inactiveprotein

Activeprotein

Cellularresponse

ATPADP

ATPADP

ATPADP

PP

PP

PP

P

P

P

P i

P i

P i

Figure 11.10

Activated relaymolecule

Phosphorylation cascade

Inactiveprotein kinase

1 Activeprotein kinase

1

Activeprotein kinase

2

Activeprotein kinase

3

Inactiveprotein kinase

2

Inactiveprotein kinase

3

Inactiveprotein

Activeprotein

ATPADP

ATPADP

ATPADP

PP

PP

PP

P

P

P i

P i

P i

P

Figure 11.10a

Cyclic AMP

• Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal

• Cholera – regulating G protein for salt and water secretion. No GTP to GDP stimulates more cAMP

• cGMP – relaxes smooth muscles – effects of viagra

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Figure 11.11

Adenylyl cyclase Phosphodiesterase

Pyrophosphate

AMP

H2O

ATP

P iP

cAMP

Calcium Ions and Inositol Triphosphate (IP3)

• Calcium is an important second messenger because cells can regulate its concentration

• Lower in cytosol than extracellular (10,000x)

• Active transport of Ca++ out or from cytosol to ER and mitochondria (IP3 and DAG)

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Figure 11.13

Mitochondrion

EXTRACELLULARFLUID

Plasmamembrane

Ca2

pump

Nucleus

CYTOSOL

Ca2

pump

Ca2

pump

Endoplasmicreticulum(ER)

ATP

ATP

Low [Ca2 ]High [Ca2 ]Key

• A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol

• Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers

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Animation: Signal Transduction Pathways

Nuclear and Cytoplasmic Responses

• regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus

• The final activated molecule in the signaling pathway may function as a transcription factor

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Figure 11.15Growth factor

ReceptorReception

Transduction

CYTOPLASM

Response

Inactivetranscriptionfactor

Activetranscriptionfactor

DNA

NUCLEUS mRNA

Gene

Phosphorylationcascade

P

Fine-Tuning of the Response

• There are four aspects of fine-tuning to consider– Amplifying the signal (and thus the response)– Specificity of the response (liver/heart)– Overall efficiency of response, enhanced by

scaffolding proteins (brain)– Termination of the signal

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Figure 11.18

Signalingmolecule

Receptor

Relay molecules

Response 1

Cell A. Pathway leadsto a single response.

Response 2 Response 3 Response 4 Response 5

Activationor inhibition

Cell B. Pathway branches,leading to two responses.

Cell C. Cross-talk occursbetween two pathways.

Cell D. Different receptorleads to a differentresponse.

Figure 11.19

Signalingmolecule

Receptor

Plasmamembrane

Scaffoldingprotein

Threedifferentproteinkinases

Concept 11.5: Apoptosis integrates multiple cell-signaling pathways

• Apoptosis is programmed or controlled cell suicide

• Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells

• Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells

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Figure 11.20

2 m

Apoptotic Pathways and the Signals That Trigger Them

• Caspases - the main proteases that carry out apoptosis

• triggered by–An extracellular death-signaling ligand –DNA damage in the nucleus–Protein misfolding in the endoplasmic

reticulum

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