11 lecture cell communication

5/26/2018 11 Lecture Cell Communication

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LECTURE PRESENTATIONS

For CAMPBELL BIOLOGY, NINTH EDITIONJane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson

2011 Pearson Education, Inc.

Lectures by

Erin Barley

Kathleen Fitzpatrick

Cell Communication

Chapter 11


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Overview: Cellular Messaging

Cell-to-cell communication is essential for bothmulticellular and unicellular organisms

Biologists have discovered some universal

mechanisms of cellular regulation

Cells most often communicate with each other

via chemical signals

For example, the fight-or-flight response is

triggered by a signaling molecule calledepinephrine



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Figure 11.1


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Concept 11.1: External signals are

converted to responses within the cell

Microbes provide a glimpse of the role of cell

signaling in the evolution of life



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Evolution of Cell Signaling

The yeast, Saccharomyces cerevisiae, has twomating types, aand

Cells of different mating types locate each othervia secreted factors specific to each type

A signal transduction pathway is a series ofsteps by which a signal on a cells surface isconverted into a specific cellular response

Signal transduction pathways convert signals ona cells surface into cellular responses



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Figure 11.2

Exchange

of mating

factors

Receptorfactor

a factorYeast cell,

mating type aYeast cell,

mating type Mating

New a/cell

1

2

3

a

a

a/


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Pathway similarities suggest that ancestralsignaling molecules evolved in prokaryotes and

were modified later in eukaryotes

The concentration of signaling molecules allows

bacteria to sense local population density



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Individual

rod-shaped

cells

Spore-forming

structure

(fruiting body)

Aggregation

in progress

Fruiting bodies

1

2

3

0.5 mm

2.5 mm

Figure 11.3


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Figure 11.3a

Individual rod-shaped cells1


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Figure 11.3b

Aggregation in progress2


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Figure 11.3c

Spore-forming structure(fruiting body)

0.5 mm

3


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Figure 11.3d

Fruiting bodies

2.5 mm


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Local and Long-Distance Signaling

Cells in a multicellular organism communicate bychemical messengers

Animal and plant cells have cell junctions that

directly connect the cytoplasm of adjacent cells

In local signaling, animal cells may communicate

by direct contact, or cell-cell recognition



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Figure 11.4Plasma membranes

Gap junctions

between animal cellsPlasmodesmata

between plant cells

(a) Cell junctions

(b) Cell-cell recognition


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In many other cases, animal cells communicateusing local regulators, messenger molecules that

travel only short distances

In long-distance signaling, plants and animals use

chemicals called hormones

The ability of a cell to respond to a signal depends

on whether or not it has a receptor specific to that

signal



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Figure 11.5

Local signaling Long-distance signaling

Target cell

Secreting

cellSecretory

vesicle

Local regulator

diffuses through

extracellular fluid.

(a) Paracrine signaling (b) Synaptic signaling

Electrical signal

along nerve cell

triggers release of

neurotransmitter.

Neurotransmitter

diffuses across

synapse.

Target cell

is stimulated.

Endocrine cellBlood

vessel

Hormone travels

in bloodstream.

Target cell

specifically

binds

hormone.

(c) Endocrine (hormonal) signaling

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Figure 11.5a

Local signaling

Target cell

Secreting

cell Secretoryvesicle

Local regulator

diffuses throughextracellular fluid.

(a) Paracrine signaling (b) Synaptic signaling

Electrical signal

along nerve cell

triggers release of

neurotransmitter.

Neurotransmitter

diffuses acrosssynapse.

Target cell

is stimulated.

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Figure 11.5b

Long-distance signaling

Endocrine cellBlood

vessel

Hormone travels

in bloodstream.

Target cell

specifically

binds

hormone.

(c) Endocrine (hormonal) signaling


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The Three Stages of Cell Signaling:

A Preview

Earl W. Sutherland discovered how the hormone

epinephrine acts on cells

Sutherland suggested that cells receiving signalswent through three processes

Reception

Transduction

Response


Animation: Overview of Cell Signaling

Fi 11 6 1
http://localhost/var/www/apps/conversion/tmp/scratch_3/11_06SignalingOverview_A.html


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Figure 11.6-1

Plasma membrane

EXTRACELLULARFLUID

CYTOPLASM

Reception

Receptor

Signaling

molecule

1

Figure 11 6 2


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Figure 11.6-2

Plasma membrane

EXTRACELLULARFLUID

CYTOPLASM

Reception Transduction

Receptor

Signaling

molecule

Relay molecules in a signal transduction

pathway

21

Figure 11 6 3


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Figure 11.6-3

Plasma membrane

EXTRACELLULARFLUID

CYTOPLASM

Reception Transduction Response

Receptor

Signaling

molecule

Activationof cellular

responseRelay molecules in a signal transduction

pathway

321


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Concept 11.2: Reception: A signaling

molecule binds to a receptor protein, causing

it to change shape

The binding between a signal molecule (ligand)

and receptor is highly specific A shape change in a receptor is often the initial

transduction of the signal

Most signal receptors are plasma membrane

proteins



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Receptors in the Plasma Membrane

Most water-soluble signal molecules bind tospecific sites on receptor proteins that span theplasma membrane

There are three main types of membrane

receptors

G protein-coupled receptors

Receptor tyrosine kinases

Ion channel receptors



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G protein-coupled receptors (GPCRs) are thelargest family of cell-surface receptors

A GPCR is a plasma membrane receptor that

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


Figure 11 7a


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Figure 11.7a

G protein-coupled receptor

Signaling molecule binding site

Segment thatinteracts withG proteins

Figure 11 7b


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Figure 11.7b

G protein-coupled

receptor

21

3 4

Plasmamembrane

G protein(inactive)

CYTOPLASMEnzyme

Activatedreceptor

Signalingmolecule

Inactiveenzyme

Activatedenzyme

Cellular response

GDPGTP

GDPGTP

GTP

P i

GDP

GDP

Figure 11.8


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Figure 11.8

Plasmamembrane

Cholesterol

2-adrenergicreceptors

Moleculeresemblingligand


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Receptor tyrosine kinases (RTKs) aremembrane receptors that attach phosphates to

tyrosines

A receptor tyrosine kinase can trigger multiple

signal transduction pathways at once

Abnormal functioning of RTKs is associated with

many types of cancers


Figure 11.7c


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g

Signaling

molecule (ligand)

21

3 4

Ligand-binding site

helix in themembrane

Tyrosines

CYTOPLASM Receptor tyrosine

kinase proteins

(inactive monomers)

Signaling

molecule

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 tyrosine

kinase regions

(unphosphorylated

dimer)

Fully activated

receptor tyrosine

kinase

(phosphorylated

dimer)

Activated relay

proteins

Cellular

response 1

Cellular

response 2

Inactive

relay proteins

6 ATP 6 ADP


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A ligand-gated ion channel receptor acts as agate 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


Figure 11.7d


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g

Signalingmolecule(ligand)

21 3

Gateclosed Ions

Ligand-gatedion channel receptor

Plasmamembrane

Gateopen

Cellularresponse

Gate closed


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Intracellular Receptors

Intracellular receptor proteins are found in thecytosol 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 2011 Pearson Education, Inc.

Figure 11.9-1C


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Hormone(testosterone)

Receptorprotein

Plasmamembrane

DNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID

Figure 11.9-2EXTRACELLULAR


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Receptorprotein

Plasmamembrane

Hormone-receptorcomplex

DNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID

Figure 11.9-3EXTRACELLULAR


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Receptorprotein

Plasmamembrane


DNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID

Figure 11.9-4

H EXTRACELLULAR


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Receptorprotein

Plasmamembrane


DNA

mRNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID

Figure 11.9-5

H EXTRACELLULAR


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Receptorprotein

Plasmamembrane

EXTRACELLULARFLUID


DNA

mRNA

NUCLEUS

CYTOPLASM

New protein


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Concept 11.3: Transduction: Cascades of

molecular interactions relay signals from

receptors to target molecules in the cell

Signal transduction usually involves multiple steps

Multistep pathways can amplify a signal: A fewmolecules can produce a large cellular response

Multistep pathways provide more opportunities for

coordination and regulation of the cellular

response



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Signal Transduction Pathways

The molecules that relay a signal from receptor toresponse are mostly proteins

Like falling dominoes, the receptor activates

another protein, which activates another, and so

on, until the protein producing the response is

activated

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

In many pathways, the signal is transmitted by a

cascade of protein phosphorylations

Protein kinases transfer phosphates from ATP toprotein, a process called phosphorylation



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Protein phosphatases remove the phosphatesfrom proteins, a process called dephosphorylation

This phosphorylation and dephosphorylation

system acts as a molecular switch, turning

activities on and off or up or down, as required


Figure 11.10


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Receptor

Signaling molecule

Activated relay

molecule

Inactiveprotein kinase

1 Activeproteinkinase

1

Activeproteinkinase

2

Activeproteinkinase

3

Inactiveprotein kinase2


3

Inactiveprotein

Activeprotein

Cellularresponse

ATPADP

ATPADP

ATPADP

PP

PP

PP

P

P

P

P i

P i

Pi

Figure 11.10a


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Activated relaymolecule


1 Activeproteinkinase

1

Activeproteinkinase

2

Activeprotein

kinase3


2


3

Inactiveprotein

Activeprotein

ATP

ADP

ATPADP

ATP

ADP

PP

PP

PP

P

P

P i

P i

P i

P


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Small Molecules and Ions as Second

Messengers

The extracellular signal molecule (ligand) that

binds to the receptor is a pathways first

messenger

Second messengers are small, nonprotein, water-

soluble molecules or ions that spread throughout a

cell by diffusion

Second messengers participate in pathwaysinitiated by GPCRs and RTKs

Cyclic AMP and calcium ions are common second

messengers 2011 Pearson Education, Inc.


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Cyclic AMP

Cyclic AMP (cAMP)is one of the most widelyused second messengers

Adenylyl cyclase, an enzyme in the plasma

membrane, converts ATP to cAMP in response to

an extracellular signal


Figure 11.11


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Adenylyl cyclase Phosphodiesterase

Pyrophosphate

AMP

H2O

ATP

P iP

cAMP

Figure 11.11a


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Adenylyl cyclase

Pyrophosphate

ATP

P iP

cAMP

Figure 11.11b


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Phosphodiesterase

AMP

H2O

cAMP

H2O


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Many signal molecules trigger formation of cAMP Other components of cAMP pathways are G

proteins, G protein-coupled receptors, and protein

kinases

cAMP usually activates protein kinase A, which

phosphorylates various other proteins

Further regulation of cell metabolism is provided

by G-protein systems that inhibit adenylyl cyclase


Figure 11.12

Fi t


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G protein

First messenger(signaling moleculesuch as epinephrine)

G protein-coupled

receptor

Adenylyl

cyclase

Secondmessenger

Cellular responses

Proteinkinase A

GTP

ATP

cAMP


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Calcium Ions and Inositol Triphosphate (IP3)

Calcium ions (Ca2+) act as a second messenger inmany pathways

Calcium is an important second messenger

because cells can regulate its concentration


Figure 11.13

EXTRACELLULAR Plasma


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Mitochondrion

EXTRACELLULARFLUID

Plasmamembrane

Ca2pump

Nucleus

CYTOSOL

Ca2pump

Ca2pump

Endoplasmicreticulum(ER)

ATP

ATP

Low [Ca2

]High [Ca2

]Key


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A signal relayed by a signal transduction pathwaymay 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


Animation: Signal Transduction Pathways

EXTRA

Figure 11.14-1
http://localhost/var/www/apps/conversion/tmp/scratch_3/11_13SignalTransduction_A.html


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G protein

EXTRA-CELLULARFLUID

Signaling molecule(first messenger)

G protein-coupledreceptor

Phospholipase C

DAG

PIP2

IP3

(second messenger)

IP3-gatedcalcium channel

Endoplasmicreticulum (ER)

CYTOSOL

Ca2

GTP

Figure 11.14-2

EXTRA


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G protein

EXTRA-CELLULARFLUID



Phospholipase C

DAG

PIP2

IP3

(second messenger)



CYTOSOL

Ca2(second

messenger)

Ca2

GTP

Figure 11.14-3

EXTRA


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G protein

EXTRA-CELLULARFLUID



Phospholipase C

DAG

PIP2

IP3

(second messenger)



CYTOSOL

Variousproteinsactivated

Cellularresponses

Ca2(second

messenger)

Ca2

GTP


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Concept 11.4: Response: Cell signaling leads

to regulation of transcription or cytoplasmic

activities

The cells response to an extracellular signal is

sometimes called theoutput response



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Nuclear and Cytoplasmic Responses

Ultimately, a signal transduction pathway leads toregulation of one or more cellular activities

The response may occur in the cytoplasm or in thenucleus

Many signaling pathways regulate the synthesis ofenzymes or other proteins, usually by turninggenes on or off in the nucleus

The final activated molecule in the signaling

pathway may function as a transcription factor


Figure 11.15Growth factor Reception


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Receptor

p

Transduction

CYTOPLASM

Response

Inactivetranscriptionfactor

Activetranscriptionfactor

DNA

NUCLEUS mRNA

Gene

Phosphorylationcascade

P


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Other pathways regulate the activity of enzymesrather than their synthesis


Figure 11.16

Reception


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Transduction

Response

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

Inactive G protein

Active G protein (102molecules)

Inactive adenylyl cyclase

Active adenylyl cyclase (102)

ATP

Cyclic AMP (104

)

Inactive protein kinase A

Active protein kinase A (104)

Inactive phosphorylase kinase

Active phosphorylase kinase (105)

Inactive glycogen phosphorylase

Active glycogen phosphorylase (106)

Glycogen

Glucose 1-phosphate(108molecules)


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Signaling pathways can also affect theoverall behavior of a cell, for example,

changes in cell shape


RESULTSFigure 11.17


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Wild type (with shmoos) Fus3 formin

Matingfactoractivatesreceptor.

Matingfactor


Shmoo projectionforming

Formin

G protein binds GTPand becomes activated.

2

1

3

4

5

P

P

P

P

ForminFormin

Fus3

Fus3Fus3

GDPGTP

Phosphory-lation

cascade

Microfilament

Actinsubunit

Phosphorylation cascadeactivates Fus3, which movesto plasma membrane.

Fus3 phos-phorylatesformin,activating it.

Formin initiates growth ofmicrofilaments that formthe shmoo projections.

CONCLUSION

Figure 11.17a


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Wild type (with shmoos)

Figure 11.17b


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Fus3

Figure 11.17c


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formin


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Fine-Tuning of the Response

There are four aspects of fine-tuning to considerAmplification of the signal (and thus the response)

Specificity of the response

Overall efficiency of response, enhanced by

scaffolding proteins

Termination of the signal



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Signal Amplification

Enzyme cascades amplify the cells response

At each step, the number of activated products is

much greater than in the preceding step



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The Specificity of Cell Signaling andCoordination of the Response

Different kinds of cells have different collections of

proteins

These different proteins allow cells to detect and

respond to different signals

Even the same signal can have different effects in

cells with different proteins and pathways

Pathway branching and cross-talkfurther helpthe cell coordinate incoming signals


Figure 11.18


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Signaling

molecule

Receptor

Relaymolecules

Response 1

Cell A. Pathway leads

to a single response.

Response 2 Response 3 Response 4 Response 5

Activation

or inhibition

Cell B. Pathway branches,

leading to two responses.

Cell C. Cross-talk occurs

between two pathways.

Cell D. Different receptor

leads to a different

response.

Signaling

Figure 11.18a


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Signalingmolecule

Receptor

Relay

molecules

Response 1

Cell A. Pathway leads

to a single response.

Response 2 Response 3

Cell B. Pathway branches,

leading to two responses.

Figure 11.18b


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Response 4 Response 5

Activation

or inhibition

Cell C. Cross-talk occurs

between two pathways.Cell D. Different receptor

leads to a different

response.

i li ffi i ff ldi i


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Signaling Efficiency: Scaffolding Proteinsand 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

In some cases, scaffolding proteins may also help

activate some of the relay proteins


Figure 11.19


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Signalingmolecule

Receptor

Plasmamembrane

Scaffoldingprotein

Threedifferentproteinkinases

T i i f h Si l


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Termination of the Signal

Inactivation mechanisms are an essential aspectof cell signaling

If ligand concentration falls, fewer receptors will be

bound

Unbound receptors revert to an inactive state


C 11 5 A i i l i l


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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


Figure 11.20


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2 m

A i i h S il W C h bditi


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Apoptosis in the Soil Worm Caenorhabditiselegans

Apoptosis is important in shaping an organism

during embryonic development

The role of apoptosis in embryonic development

was studied in Caenorhabditis elegans

In C. elegans, apoptosis results when proteins that

accelerateapoptosis override those that put the

brakeson apoptosis


Figure 11.21


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Mitochondrion

Ced-9

protein (active)inhibitsCed-4activity

Receptorfor death-signaling

molecule

Ced-4 Ced-3

Inactive proteins

(a) No death signal

Death-signalingmolecule

Ced-9(inactive)

Cellformsblebs

ActiveCed-4

ActiveCed-3

Otherproteases

NucleasesActivationcascade

(b) Death signal

Figure 11.21a

Ced-9


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Mitochondrion

protein (active)inhibitsCed-4activity

Receptorfor death-signalingmolecule

Ced-4 Ced-3

Inactive proteins

(a) No death signal

Ced-9 Cell

Figure 11.21b


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Death-signalingmolecule

Ced 9(inactive)

Cellformsblebs

ActiveCed-4

ActiveCed-3

Otherproteases

Nucleases

Activationcascade

(b) Death signal

A t ti P th d th Si l Th t


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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



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Apoptosis evolved early in animal evolution and isessential for the development and maintenance of

all animals

Apoptosis may be involved in some diseases (for

example, Parkinsons and Alzheimers);interference with apoptosis may contribute to

some cancers


Figure 11.22


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Interdigital tissue

Cells undergoingapoptosis

Space betweendigits1 mm

Figure 11.22a


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Interdigital tissue

Figure 11.22b


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Cells undergoingapoptosis

Figure 11.22c


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Space betweendigits1 mm

Figure 11.UN01


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Reception1 2 3Transduction Response

Receptor

Signalingmolecule

Relay molecules

Activation

of cellularresponse

Figure 11.UN02


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11 lecture cell communication

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