Chap 9 Basics Notes

8/11/2019 Chap 9 Basics Notes

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Efficient communication is vital

Cells need to communicate with each other, coordinate responses (e.g.devo)

Need to respond to changing environment

Communication within cells

Chap 9 Basics Cell communication

Two examples of cell response to stimuli:information must perceived and cell responses

organized


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3 stages of cell signaling1.

Receptor activation

Signaling molecule binds to receptor

2.

Signal transduction

Activated receptor stimulates sequence of changes- signaltransduction pathway

3.

Cellular response

Several different responses

Alter activity of 1 or more enzymes

Alter structural protein function

Change gene expression

Ligand

Signaling molecule

Binds noncovalentlyto receptor with high degree of specificity/affinity: affinity described by Kd (dissociation constant similar to

Km but ligand is NOT a substrate)

Binding and release between receptor and ligand relatively rapid

Ligands alter receptor structure- conformational change (activation/

inhibition)


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Signal transductionpathway

Inactivereceptor protein

Receptor activation: The binding of a signallingmolecule causes a conformational change in a

receptor that activates its function.

1 Cellular response: The signal transduction pathway affects the functionsand/or amounts of cellular proteins, thereby producing a cellular response.

3

Signal transduction: Theactivated receptor stimulates a

series of proteins that forms a

signal transduction pathway.

2 Altered metabolism or otherCell functions

Altered cell shape ormovement

Altered gene expression,Which changes the types

and the amounts of proteins

in the cell

Transcriptionfactor

Structuralprotein

Enzyme

Cellularresponse

Intracellulartargets

Activatedreceptor

protein

Nucleus

Signallingmolecule

Typical signal transduction pathway


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The binding of a ligand to its receptor causes aconformational change in the receptor, resulting

in receptor activation.

Ligand (signalling molecule)

Inactivereceptor

Cytosol

Activatedreceptor


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Cell surface receptors

1. Enzyme-linked receptors

Found in all living species

Extracellular domain binds signal

Causes intracellular domain to become

functional catalyst

Many are protein kinases


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2. G-protein coupled receptors(GPCR)

Common in most eukaryotes (though not plants)

Protein contains 7 transmembrane domains

NOT catalytic

Activated receptor binds to G protein

G-protein releases GDP and binds GTP instead

GTP causes G-protein to disassociate

!-subunit and "/#dimer interact with other

proteins in a signaling pathway

GPCRs very important in animals (vision, smell,

immune responses, behaviour, etc.)

targets of many pharmacological drugs


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The G protein exchanges GDP for GTP. The G protein then

dissociates from the receptor and separates into an active!subunit and a "/#dimer. The activated subunits promote

cellular responses.

Receptor

protein

(GPCR)

"

#

The signalling molecule eventually dissociates from the receptor,

and the subunit hydrolyzes GTP into GDP + Pi. The !subunit and

the "/#dimer reassociate.

3

1 A signalling molecule binds to aGPCR, causing it to bind to aG protein.

+

2

signalling

molecule

Activated

G protein

!subunitActivated

G protein

"/#dimer

GDP

Inactive G

protein

Cytosol

GTP

GDP

released

!

Pi


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3.

Ligand-gated ion channels

Plant and animal cells

Ligand binding causes ion channels to open and ions to flow

through the membrane

Animals- signals between nerve and muscle cells, between 2

nerve cells, Ca2+uptake


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Intracellular receptors

Many receptors on the plasma membrane but some are inside the cell

Estrogen example (mammalian hormone)

Passes through membrane (why?) and binds to receptor in nucleus

Dimer of estrogen-receptor complexes binds to DNA to activatetranscription of specific genes

Transcription factors regulate transcription of specific genes


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Second messengers

Signals binding to cell surface are firstmessenger

Many signal transduction pathways lead to

production of second messengers Examples

cAMP

Ca2+ Diacylglycerol and inositol triphosphate (IP3)


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Signal transduction via cAMP

Cyclic adenosine monophosphate

Ligand binding to GPCR activates G protein to

bind GTP causing dissociation

One type of subunit binds to adenylyl cyclasestimulating synthesis of cAMP

One effect of cAMP is to activate protein kinase

A (PKA)

Activated catalytic PKA subunits phosphorylates

specific cellular proteins

When signaling molecules no longer produced,

eventually effects of PKA reversed


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cAMP has 2 advantages1.

Signal amplification binding of signal to single receptor can causethe synthesis of many cAMP that activate PKA, each PKA canphosphorylate many proteins

2.

Speed in one experiment a substantial amount of cAMP was madewithin 20 seconds after addition of signal


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AMPLIFICATION AND PROPAGATION(SIGNALLING IN GENERAL, NOT JUST VIA cAMP)


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Signal transduction via Ca2+

Cells maintain a very large Ca2+gradient

2 types of calcium pumps

When calcium channels open, influx of Ca2+acts as a second messenger

Plants- phototropism, opening and closing

of stomata, gravitropism, stress responseAnimals- nerve transmission, muscle

contraction, secretion of digestive enzymes


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A cells response to signaling molecules

depends on the proteins it makes

One hormone causes different effects indifferent cell types

Differential gene expression- all cells containthe same genome but only express particularparts

Can effect cellular response in a variety ofways

Receptor not expressed, different receptors forsame signal, different affinities for signal, signaltransduction pathways different, proteinexpression different


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Take Home Points

cell communication is about information processing

processing is both inter- and intracellular

3 stages: (i) detection, (ii) signal transduction (ST), (iii) physiologicalresponse(s)

there are 5 main classes of intercellular signaling

receptors are at the top of the hierarchy (i.e. detection pt)

understand concepts of ligand, Kd

protein conformational changes very important

second messengers are used to amplify and propagate information

ST pathways are regulated, often by kinases/phosphatases there are

specific ways to activate and inactivate ST pathways

activation of ST pathways often leads to changes in: gene/proteinexpression, enzyme activities, developmental programs, etc. all specific

to the activation signal (e.g. hormone X, pathogen Y, etc.)

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Chap 9 Basics Notes