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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