Fig. 11-3 Chapter 11 Cell Communication. Please note that due to differing operating systems, some animations will not appear until the presentation is

Fig. 11-3

Chapter 11Cell Communication

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Concept 11.1: External signals are converted to responses

within the cell• Microbes are a window on the role of cell signaling in the evolution of life

• A signal transduction pathway converts signals on a cell’s surface into cellular responses

Yeast cell,mating type a

Yeast cell,mating type

New a/cellFig. 11-2

Fig. 11-5

Local signaling

Target cell

Secretingcell

Secretoryvesicle

Local regulatordiffuses throughextracellular fluid

(a) Paracrine signaling (b) Synaptic signaling

Target cellis stimulated

Neurotransmitter diffuses across synapse

Electrical signalalong nerve celltriggers release ofneurotransmitter

Long-distance signaling

Endocrine cell Bloodvessel

Hormone travelsin bloodstreamto target cells

Targetcell

(c) Hormonal signaling

Local and Long-Distance Signaling

The Three Stages of Cell Signaling:• Earl W. Sutherland discovered how the hormone

epinephrine acts on cells• Earl W. Sutherland, Jr. –The Nobel Foundation. http://nobelprize.org/medicine/laureates/1971/sutherland-cv.html.

• Sutherland suggested that cells receiving signals went through three processes:– Reception– Transduction– Response

http://nobelprize.org/medicine/laureates/1971/sutherland-cv.html

http://nobelprize.org/medicine/laureates/1971/sutherland-cv.html

Fig. 11-6-1

Reception1

EXTRACELLULARFLUID

Receptor

Signalingmolecule

Plasma membrane

CYTOPLASM

1

Fig. 11-6-2

Reception1

EXTRACELLULARFLUID

Receptor

Signalingmolecule

Plasma membrane

CYTOPLASM

1

Relay molecules in a signal transduction pathway

Transduction2

Fig. 11-6-3

EXTRACELLULARFLUID

Plasma membrane

CYTOPLASM

Receptor

Signalingmolecule

Relay molecules in a signal transduction pathway

Activationof cellularresponse

Reception Transduction Response1 2 3

Receptors in the Plasma Membrane

• Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane

• There are three main types of membrane receptors:– G protein-coupled receptors– Receptor tyrosine kinases– Ion channel receptors

Fig. 11-7a

Signaling-molecule binding site

Segment thatinteracts withG proteins

G protein-coupled receptor

Fig. 11-7b

G protein-coupledreceptor

Plasmamembrane

EnzymeG protein(inactive)

GDP

CYTOPLASM

Activatedenzyme

GTP

Cellular response

GDP

P i

Activatedreceptor

GDP GTP

Signaling moleculeInactiveenzyme

1 2

3 4

• Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines

• A receptor tyrosine kinase can trigger multiple signal transduction pathways at once

Fig. 11-7c

Signalingmolecule (ligand)

Ligand-binding site

Helix

TyrosinesTyr

Tyr

Tyr

Tyr

Tyr

Tyr

Receptor tyrosinekinase proteins

CYTOPLASM

Signalingmolecule

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Dimer

Activated relayproteins

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

P

P

P

P

P

P

Cellularresponse 1

Cellularresponse 2

Inactiverelay proteins

Activated tyrosinekinase regions

Fully activated receptortyrosine kinase

6 6 ADPATP

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

P

P

P

P

P

P

1 2

3 4

• 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

Fig. 11-7d Signalingmolecule(ligand)

Gateclosed Ions

Ligand-gatedion channel receptor

Plasmamembrane

Gate open

Cellularresponse

Gate closed3

2

1

Intracellular Receptors

• found in the cytosol or nucleus of target cells

• Small or hydrophobic chemical messengers

• Examples : the steroid and thyroid hormones of animals

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

Fig. 11-8-1 Hormone(testosterone)

Receptorprotein

Plasmamembrane

EXTRACELLULARFLUID

DNA

NUCLEUS

CYTOPLASM

Fig. 11-8-2

Receptorprotein

Hormone(testosterone)

EXTRACELLULARFLUID

Plasmamembrane

Hormone-receptorcomplex

DNA

NUCLEUS

CYTOPLASM


EXTRACELLULARFLUID

Receptorprotein

Plasmamembrane


DNA

NUCLEUS

CYTOPLASM


EXTRACELLULARFLUID

PlasmamembraneReceptor

protein


DNA

mRNA

NUCLEUS

CYTOPLASM


EXTRACELLULARFLUID

Receptorprotein

Plasmamembrane


DNA

mRNA

NUCLEUS New protein

CYTOPLASM

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

• involves multiple steps• amplify a signal: A few molecules can produce a large cellular response

• provide more opportunities for coordination and regulation of the cellular response

23

Phosphorylation is key in control of protein

function• Addition of phosphate group• A cell’s response to a signal often involves activating or inactivating proteins

• Phosphorylation is a common way to change the activity of a protein– Protein kinase – an enzyme that adds a phosphate to a protein

– Phosphatase – an enzyme that removes a phosphate from a protein

• This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off

Fig. 11-9

Signaling molecule

ReceptorActivated relaymolecule

Inactiveprotein kinase

1 Activeproteinkinase

1


2

ATPADP Active

proteinkinase

2

P

PPP


3

ATPADP Active

proteinkinase

3

P

PPP

i

ATPADP P

ActiveproteinPP

P i

Inactiveprotein

Cellularresponse

Phosphorylation cascadei

usually involves multiple steps

can amplify a signal

usually a shape change

by a cascade of protein phosphorylations

provide coordination and regulation of the cellular response

Second Messengers

• The extracellular signal molecule : “first messenger”

• Second messengers are small, nonprotein, water-soluble molecules or ions

• participate in pathways initiated by G protein-coupled receptors and receptor tyrosine kinases

• Cyclic AMP and calcium ions are common second messengers

Adenylyl cyclase

Fig. 11-10

Pyrophosphate

P P i

ATP cAMP

Phosphodiesterase

AMP

Cyclic AMP (cAMP) is one of the most widely used second messengersAdenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response

to an extracellular signal

First messengerFig. 11-11

G protein

Adenylylcyclase

GTP

ATP

cAMPSecondmessenger

Proteinkinase A

G protein-coupledreceptor

Cellular responses

EXTRACELLULARFLUID

Fig. 11-12

ATP

Nucleus

Mitochondrion

Ca2+ pump

Plasmamembrane

CYTOSOL

Ca2+

pumpEndoplasmicreticulum (ER)

Ca2+

pumpATP

Key

High [Ca2+]

Low [Ca2+]

Calcium Ions and Inositol Triphosphate (IP3)

Nuclear and Cytoplasmic Responses• Ultimately, a signal transduction

pathway leads to regulation of one or more cellular activities

• The response may occur in the cytoplasm or may involve action in the nucleus

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

• The final activated molecule may function as a transcription factor

Fig. 11-13-1

EXTRA-CELLULARFLUID

Signaling molecule(first messenger)

G protein

GTP

G protein-coupledreceptor Phospholipase C PIP2

IP3

DAG

(second messenger)

IP3-gatedcalcium channel

Endoplasmicreticulum (ER) Ca2+

CYTOSOL

Fig. 11-13-2

G protein

EXTRA-CELLULARFLUID



DAG

IP3

(second messenger)



CYTOSOL

Ca2+

(secondmessenger)

GTP

Fig. 11-13-3

G protein

EXTRA-CELLULARFLUID



DAG

IP3

(second messenger)



CYTOSOL

Variousproteinsactivated

Cellularresponses

Ca2+

(secondmessenger)

GTP

33

Adenylyl cyclase

Phosphatidylinositol 4,5-bisphosphate

http://en.wikipedia.org/wiki/Phosphatidylinositol_4,5-bisphosphate

Fig. 11-14Growth factor

Receptor

Phosphorylationcascade

Reception

Transduction

Activetranscriptionfactor

ResponseP

Inactivetranscriptionfactor

CYTOPLASM

DNA

NUCLEUS mRNA

Gene

Fig. 11-15

Reception

Transduction

Response

Binding of epinephrine to G protein-coupled receptor (1 molecule)

Inactive G protein

Active G protein (102 molecules)

Inactive adenylyl cyclaseActive adenylyl cyclase (102)

ATPCyclic AMP (104)

Inactive protein kinase AActive protein kinase A (104)

Inactive phosphorylase kinase

Active phosphorylase kinase (105)

Inactive glycogen phosphorylase

Active glycogen phosphorylase (106)

GlycogenGlucose-1-phosphate

(108 molecules)

37

Fig. 11-16a

RESULTS

Wild-type (shmoos) ∆Fus3 ∆formin

How do signals induce directional cell growth in yeast?

Fig. 11-16b

CONCLUSION

Matingfactor G protein-coupled

receptor

GDPGTP

Phosphory- lation cascade

Shmoo projectionforming

Fus3

Fus3 Fus3

Formin Formin

P

P

P

ForminP

Actinsubunit

Microfilament

1

2

3

4

5

Fig. 11-17

Signalingmolecule

Receptor

Relaymolecules

Response 1

Cell A. Pathway leadsto a single response.

Response 2 Response 3

Cell B. Pathway branches,leading to two responses.


Activationor inhibition

Cell C. Cross-talk occursbetween two pathways.

Cell D. Different receptorleads to a different response.

The Specificity of Cell Signaling and

Coordination of the Response

Fig. 11-17a

Signalingmolecule

Receptor

Relaymolecules

Response 1

Cell A. Pathway leadsto a single response.

Cell B. Pathway branches,leading to two responses.


Fig. 11-17b


Activationor inhibition

Cell C. Cross-talk occursbetween two pathways.

Cell D. Different receptorleads to a different response.

Signaling Efficiency: Scaffolding Proteins and Signaling

Complexes

• Scaffolding proteins are large relay proteins to which other relay proteins are attached

• Scaffolding proteins can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway

Fig. 11-18

Signalingmolecule

Receptor

Scaffoldingprotein

Plasmamembrane

Threedifferentproteinkinases

Fig. 11-UN1

Reception Transduction Response

Receptor

Relay molecules

Signalingmolecule

Activationof cellularresponse

1 2 3

Concept 11.5: Apoptosis (programmed cell death) integrates multiple cell-signaling pathways

• Apoptosis is programmed or controlled cell suicide

• A cell is chopped and packaged into vesicles that are digested by scavenger cells

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

Fig. 11-19

2 µm

Apoptosis in the Soil Worm Caenorhabditis elegans

• Apoptosis is important in shaping an organism during embryonic development

• The role of apoptosis in embryonic development was first studied in Caenorhabditis elegans

• In C. elegans, apoptosis results when specific proteins that “accelerate” apoptosis override those that “put the brakes” on apoptosis

Fig. 11-20

Ced-9protein (active)inhibits Ced-4activity

Mitochondrion

Receptorfor death-signalingmolecule

Ced-4 Ced-3

Inactive proteins

(a) No death signal

Ced-9(inactive)

Cellformsblebs

Death-signalingmolecule

Otherproteases

ActiveCed-4

ActiveCed-3

NucleasesActivationcascade

(b) Death signal

Fig. 11-20a

Ced-9protein (active)inhibits Ced-4activity

Mitochondrion

Ced-4 Ced-3Receptorfor death-signalingmolecule

Inactive proteins

(a) No death signal

Fig. 11-20b

(b) Death signal

Death-signalingmolecule

Ced-9(inactive)

Cellformsblebs

ActiveCed-4

ActiveCed-3

Activationcascade

Otherproteases

Nucleases

Apoptotic Pathways and the Signals That Trigger Them

• Caspases are the main proteases (enzymes that cut up proteins) that carry out apoptosis

• Apoptosis can be triggered by:– An extracellular death-signaling ligand – DNA damage in the nucleus– Protein misfolding in the endoplasmic reticulum

• Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals

• Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers

Fig. 11-21

Interdigital tissue 1 mm

You should now be able to:1. Describe the nature of a ligand-receptor

interaction and state how such interactions initiate a signal-transduction system

2. Compare and contrast G protein-coupled receptors, tyrosine kinase receptors, and ligand-gated ion channels

3. List two advantages of a multistep pathway in the transduction stage of cell signaling

4. Explain how an original signal molecule can produce a cellular response when it may not even enter the target cell

5. Define the term second messenger; briefly describe the role of these molecules in signaling pathways

6. Explain why different types of cells may respond differently to the same signal molecule

7. Describe the role of apoptosis in normal development and degenerative disease in vertebrates

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Fig. 11-3 Chapter 11 Cell Communication. Please note that due to differing operating systems, some animations will not appear until the presentation is