bio 11 campbell

8/10/2019 bio 11 campbell

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Overview: Cellular Messaging

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

Biologists have discovered some universalmechanisms of cellular regulation

Cells most often communicate with each othervia chemical signals

For example, the fight-or-flight response istriggered by a signaling molecule calledepinephrine

2011 Pearson Education, Inc.


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Cellularcommunication

Types of signaling Contact

Local

Paracrine Synaptic

Long-distance

Endocrinesystem: viahormones

Neuronal: viaelctricity


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Local

Paracrine Synaptic

Long-distance




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Local

Paracrine Synaptic

Long-distance




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Local

Paracrine Synaptic

Long-distance


Neuronal: viaelectricity


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Figure 11.1


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Concept 11.1: External signals are convertedto responses within the cell

Concept 11.2: Reception: A signalingmolecule binds to a receptor protein, causingit to change shape

Concept 11.3: Transduction: Cascades of

molecular interactions relay signals fromreceptors to target molecules in thecellConcept

11.4: Response: Cell signaling leads toregulation of transcription or cytoplasmicactivities

Concept 11.5: Apoptosis integrates multiple cell-signalingpathways


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Concept 11.1: External signals areconverted to responses within the cell

Microbes provide a glimpse of the role of cellsignaling in the evolution of life



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Evolution of Cell Signaling

The yeast, Saccharomyces cerevisiae , has twomating types, a and

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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C o m m u n i c a t i on be tweenm at ing yeas tcel ls

How canthis be

analogizedtopeople?

Exchangeof matingfactors

Receptor factor

a factor Yeast cell,mating type a

Yeast cell,mating type

Mating

New a/ cell

1

2

3

a

a

a/


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How could we find out how long ago cellcommunication evolved?



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How could we find out how long ago cellcommunication evolved?

See if similar mechanisms are present in bacteriaand recently developed organisms like people.



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Individualrod-shapedcells

Spore-formingstructure(fruiting body)

Aggregationin progress

Fruiting bodies

1

2

3

0.5 mm

2.5 mm

The concentration ofsignaling moleculesallows bacteria to senselocal population density


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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 11.4 Plasma membranes

Gap junctionsbetween animal cells

Plasmodesmatabetween plant cells

(a) Cell junctions

(b) Cell-cell recognition


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Figure 11.5a

Local signaling

Target cell

Secretingcell Secretoryvesicle

Local regulatordiffuses throughextracellular fluid.

(a) Paracrine signaling using local regulators(b) Synaptic signaling withneurotransmitters

Electrical signalalong nerve celltriggers release ofneurotransmitter.

Neurotransmitter

diffuses acrosssynapse.

Target cellis stimulated.


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Figure 11.5b

Long-distance signaling

Endocrine cell Bloodvessel

Hormone travelsin bloodstream.

Target cellspecificallybindshormone.

(c) Endocrine (hormonal) signaling


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The Three Stages of Cell Signaling:

1. Reception2. Transduction

3. Response



19/69 2011 Pearson Education, Inc.

Animation: Overview of Cell SignalingRight- click slide / select Play

Fi 11 6 1


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Figure 11.6-1

Plasma membraneEXTRACELLULARFLUID

CYTOPLASM

Reception

Receptor

Signalingmolecule

1

Fi 11 6 2


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Figure 11.6-2


CYTOPLASM

Reception Transduction

Receptor

Signalingmolecule

Relay molecules in a signal transductionpathway

2 1

Fig 11 6 3


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Figure 11.6-3


CYTOPLASM

Reception Transduction Response

Receptor

Signalingmolecule

Activationof cellularresponse

Relay molecules in a signal transductionpathway

3 2 1


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Concept 11.2: Reception: A signalingmolecule binds to a receptor protein, causingit to change shape



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Receptors in the Plasma Membrane

There are three main types of membranereceptors

1. G protein-coupled receptors2. Receptor tyrosine kinases3. Ion channel receptors


G i l d (GPCR ) h l f il f ll


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G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptorsThe G protein acts as an on/off switch: If GDP is bound to the Gprotein, the G protein is inactive

G protein-coupled receptor

Signaling molecule binding site

Segment thatinteracts withG proteins

Figure 11 7b


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Figure 11.7b

G protein-coupledreceptor

2 1

3 4

Plasmamembrane

G protein(inactive)

CYTOPLASM Enzyme

Activatedreceptor

Signalingmolecule

Inactiveenzyme

Activatedenzyme

Cellular response

GDPGTP

GDPGTP

GTP

P i

GDP

GDP

Note: the enzyme is activatedby shape change


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Figure 11.8: The sturcutre of a G Protien-Coupled Receptor

Plasmamembrane

Cholesterol

2-adrenergicreceptors

Moleculeresemblingligand

2 Receptor tyrosine kinase


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2. Receptor tyrosine kinase

Signalingmolecule (ligand)

2 1

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(phosphorylated

dimer)

Activated relayproteins

Cellularresponse 1

Cellularresponse 2

Inactiverelay proteins

6 ATP 6 ADP


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

Benefit: A receptor tyrosine kinase can triggermultiple signal transduction pathways at once

Tidbit: Abnormal functioning of RTKs is associatedwith many types of cancers


Figure 11.7d


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g .

Signalingmolecule(ligand)

2 1 3

Gateclosed Ions

Ligand-gatedion channel receptor

Plasmamembrane

Gateopen

Cellularresponse

Gate closed

A ligand-gated ion channel receptor acts as a gate when thereceptor changes shapeWhen a ligand binds to the receptor, the gate allows specific

ions, such as Na+ or Ca

2+, through a channel in the receptor


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Intracellular Receptors

Intracellular receptor proteins are found in thecytosol or nucleus of target cells

Small or hydrophobic chemical messengerscan readily cross the membrane and activatereceptors Examples of hydrophobic messengers are the

steroid and thyroid (lipid soluble) hormones ofanimals


Figure 11.9-1


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gHormone(testosterone)

Receptorprotein

Plasmamembrane

DNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID

Figure 11.9-2


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gHormone(testosterone)

Receptorprotein

Plasmamembrane

Hormone-receptorcomplex

DNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID

Figure 11.9-3


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Hormone(testosterone)

Receptorprotein

Plasmamembrane


DNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID

Figure 11.9-4


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Receptorprotein

Plasmamembrane


DNA

mRNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID

Figure 11.9-5


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Receptorprotein

Plasmamembrane

EXTRACELLULARFLUID


DNA

mRNA

NUCLEUS

CYTOPLASM

New protein


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Concept 11.3: Transduction: Cascades ofmolecular interactions relay signals fromreceptors to target molecules in the cell

Signal transduction usually involves multiple steps

What are some benefits of a multistep pathwaya.k.a. cascade?



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Concept 11.3: Transduction: Cascades ofmolecular interactions relay signals fromreceptors to target molecules in the cell

Signal transduction usually involves multiple steps,

a.k.a. cascade? Benefit 1: can amplify a signal: (A few moleculescan produce a large cellular response)

Benefit 2: provide more opportunities for

coordination and regulation of the cellular response



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Protein Phosphorylation andDephosphorylation is the cascades signal

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

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

Inactiveprotein kinase

3

Inactiveprotein

Activeprotein

Cellularresponse

ATPADP

ATPADP

ATPADP

PP

PP

PP

P

P

P

P i

P i

Pi

upstream/downstreamregulation


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Small Molecules and Ions as SecondMessengers

The extracellular signal molecule (ligand) thatbinds to the receptor is a pathways firstmessenger

Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout acell by diffusion

Cyclic AMP and calcium ions are common secondmessengers


Figure 11.11


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Adenylyl cyclase Phosphodiesterase

Pyrophosphate

AMP

H2O

ATP

P i P

cAMP

What other organic molecule docAMP resemble?

Why?

Figure 11.12


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G protein

First messenger(signaling moleculesuch as epinephrine)

G protein-coupled

receptor

Adenylyl

cyclase

Secondmessenger

Cellular responses

Proteinkinase A

GTP

ATPcAMP


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Calcium I ons and I nosi tol Tr iphosphate (I P 3 )

Calcium ions (Ca 2+) act as a second messenger inmany pathways

Calcium is an important second messengerbecause cells can regulate its concentration


Figure 11.13

l


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Mitochondrion

EXTRACELLULARFLUID

Plasmamembrane

Ca 2 pump

Nucleus

CYTOSOL

Ca 2 pump

Ca 2 pump

Endoplasmicreticulum(ER)

ATP

ATP

Low [Ca2

]High [Ca2

]Key


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Animation: Signal Transduction PathwaysRight- click slide / select Play

Figure 11.14-1: Calcium and IP 3 in signaling pathways


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G protein

EXTRA-CELLULARFLUID

Signaling molecule(first messenger)

G protein-coupledreceptor Phospholipase C

DAG

PIP 2

IP 3(second messenger)

IP 3-gatedcalcium channel

Endoplasmicreticulum (ER)

CYTOSOL

Ca 2

GTP

Figure 11.14-2


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G protein

EXTRA-CELLULARFLUID



DAG

PIP 2




CYTOSOL

Ca 2 (second

messenger)

Ca 2

GTP

Figure 11.14-3


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G protein

EXTRA-CELLULARFLUID



DAG

PIP 2




CYTOSOL

Variousproteinsactivated

Cellularresponses

Ca 2 (second

messenger)

Ca 2

GTP


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Concept 11.4: Response: Cell signaling leads toregulation of transcription or cytoplasmicactivities

The final activated molecule in the signalingpathway may have a response in the cytoplasm(e.g. changing shape of cytoskeleton or regulatingenzymes) or function as a transcription factor


Figure 11.15Growth factor Reception


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ReceptorReception

Transduction

CYTOPLASM

Response

Inactivetranscriptionfactor

Activetranscriptionfactor

DNA

NUCLEUS mRNA

Gene

Phosphorylationcascade

P

Reception


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Cytoplasmicresponse to asignal:the stimulationof glycogen

breakdown byepinephrine.

Reception

Transduction

Response

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

Inactive G protein

Active G protein (10 2 molecules)

Inactive adenylyl cyclaseActive adenylyl cyclase (10 2)

ATP

Cyclic AMP (104)

Inactive protein kinase AActive protein kinase A (10 4)

Inactive phosphorylase kinaseActive phosphorylase kinase (10 5)

Inactive glycogen phosphorylaseActive glycogen phosphorylase (10 6)

GlycogenGlucose 1-phosphate

(10 8 molecules)


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


RESULTS


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Wild type yeast (with shmoos) Fus3 formin

Matingfactoractivatesreceptor.

Matingfactor G protein-coupled

receptor

Shmoo projectionforming

Formin

G protein binds GTPand becomes activated.

2

1

3

4

5

P

P

P

PForminFormin

Fus3

Fus3Fus3

GDP GTPPhosphory-

lationcascade

Microfilament

Actinsubunit

Phosphorylation cascadeactivates Fus3, which movesto plasma membrane.

Fus3 phos-phorylatesformin,activating it.

Formin initiates growth ofmicrofilaments that formthe shmoo projections.

CONCLUSION

What is this showing?

Figure 11.17a


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Wild type (with shmoos)


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Fine-Tuning of the Response

There are four aspects of fine-tuning to consider:1. Amplification of the signal (and thus the

response)2. Specificity of the response3. Overall efficiency of response, enhanced by

scaffolding proteins4. Termination of the signal



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Signal Amplif ication

Enzyme cascades amplify the cells response At each step, the number of activated products is

much greater than in the preceding step


Figure 11.18 The specificity of cell signaling.


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Signaling

molecule

Receptor

Relaymolecules

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

Signaling Efficiency: Scaffolding Proteins


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Signalingmolecule

Receptor

Plasmamembrane

Scaffoldingprotein

Threedifferentprotein

kinases

g g y: gand Signaling Complexes


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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



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Concept 11.5: Apoptosis integrates multiplecell-signaling pathways

Apoptosis is programmed or controlled cellsuicide

WHY IS THIS FUNCTION CRITICAL?



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Concept 11.5: Apoptosis integrates multiplecell-signaling pathways

Apoptosis is programmed or controlled cellsuicide

Components of the cell are chopped up andpackaged into vesicles that are digested byscavenger cells

Apoptosis prevents enzymes from leaking out of a

dying cell and damaging neighboring cells


Figure 11.20: white blood cell apoptosis


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2 m


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Apoptosis in the Soil Worm Caenorhabditiselegans

Apoptosis is important in shaping an organismduring embryonic development

The role of apoptosis in embryonic developmentwas studied in Caenorhabditis elegans

In C. elegans , apoptosis results when proteins thataccelerate apoptosis override those that put the

brakes on apoptosis


Figure 11.21


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Mitochondrion

Ced-9

protein (active)inhib i t s Ced-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


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Apoptotic Pathways and the Signals ThatTrigger Them

Caspases are the main proteases ( what arethese? ) 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 may be involved in some diseases (forexample, Parkinsons and Alzheimers);interference with apoptosis may contribute tosome cancers



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Figure 11.22: apoptosis in paw development of the mouse

Interdigital tissueCells undergoing

apoptosisSpace between

digits1 mm


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REVIEW

Reception1 2 3 Transduction Response

Receptor

Signaling

molecule

Relay molecules

Activation

of cellularresponse

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