Download - CELL COMMUNICATION
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CAMPBELL & REECECHAPTER 11
CELL COMMUNICATION
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Cell Messaging
some universal mechanisms of cellular regulation
cells most often communicate with other cells by chemical signals
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Evolution of Cell Signaling
Yeast: Saccharomyces cerevisia2 sexes: a & αtype a secrete a signaling molecule
called “a factor” which can bind to receptor proteins on α cells
@ same time α cells secrete “α factor” which binds to receptor proteins on type a cells
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Saccharomyces cerevisiae
2 mating factors then cause the 2 yeast cells to grow toward each other & initiate other cell changes
results in fusion or mating of 2 cells of opposite type a/α cell that contains genes of both original cells
this new cell later divides passing this genetic combination to their offspring
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Signal Transduction Pathway
series of steps initiated by signal molecule attaching to receptor
mechanism similar in yeasts and mammals & between bacteria and plants
Scientists think signaling mechanisms 1st evolved in ancient prokaryotes & unicellular eukaryotes then adopted for new uses by their multicellular descendants
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Communication Among Bacteria
quorum sensing: bacteria release small molecules detected by like bacteria: gives them a “sense” of local density of cells
allows them to coordinate activities only productive when performed by given # in synchrony
ex: forming a biofilm: aggregation of bacteria adhered to a surface: slime on fallen leaves or on your teeth in the morning (they cause cavities)
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Biofilm Developing
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Biofilm Development
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Local Signaling
(eukaryotic cells can also use cell junctions)
secretion of chemicals = messenger molecules from signaling cell
messenger molecules that travel to nearby cells only called: local regulators
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Local Regulators
Animals: use 1 class of local regulators: growth factors
many cells in neighborhood respond to growth factor produced by 1 cell
paracrine signaling: secreting cell acts on nearby target cells by discharging local regulator
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Paracrine Signaling
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Synaptic Signaling
in the animal nervous systemaction potential travels thru cell
membrane of neuron when the electrical signal reaches axon end it triggers exocytosis of neurotransmitter (messenger molecule)
neurotransmitter travels across small space (synapse) attaches to receptors on target cell
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Synaptic Signaling
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Local Signaling in Plants
not as well understood as in animalsuse hormones (as do animals): long
distance signaling aka endocrine signaling travel target cells (any cell that has
receptor for hormone)Plant hormones aka plant growth
regulatorsmost reach their targets by moving
cell-to-cellsome travel in vessels
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Long Distance Signaling
hormones (in some cases)
neurotransmitters: electrical signal travels length of neuron, may go from neuron-to-neuron for long distances
ability for any cell to respond to messenger molecule requires cell to have receptor for that particular molecule
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3 Stages of Cell Signaling
1. Reception target cell’s detection of the signal
2. Transduction receptor protein changes converting
signal to a form that can bring about specific cellular response via a signal transduction pathway
3. Response activation of cellular response
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Stages of Cell Signaling Response
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Reception
cells must have a receptor for the ligand (messenger molecule) to react with
many signal receptors are transmembrane proteins with water-soluble ligandsligands:
usually large hydrophilic
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Membrane Receptors
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G-Protein-Coupled Receptors
cell-surface transmembrane receptorworks with help of a G protein (protein
that binds to GTP)flexible inherently unstable
difficult to crystallize so can study structure (use x-ray crystallography)
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G Protein-Coupled Receptor: 7 α helices
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Receptor Tyrosine Kinases
major class of membrane receptors w/enzyme activity
kinase: enzyme that catalyzes addition of phosphate group
cytoplasmic side of receptor has enzyme that: phosphate group from ATP tyrosine (on substrate protein)
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Tyrosine
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Inactive Monomers of Tyrosine Kinase
When there is no ligand attached to receptor site the kinase receptor protein exists as monomers
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Binding of Signaling Molecule: Form Dimers
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Tyrosine Kinase Activated by Dimerization
phosphate group added to each tyrosine
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Recognition by Relay ProteinsRelay proteins
attach to phosphorylated tyrosine structural change that activates the bound protein
Each activated relay protein triggers different transduction pathway specific cellular response
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ION CHANNEL RECEPTORS
Ligand-Gated Ion Channels
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Ligand Binds to Receptor Site
ion crosses membrane & enters cytoplasm transduction pathway leading to a response
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Ligand Dissociates from Receptor Site
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Intracellular Receptors
in cytoplasm or nucleus of target cellshydrophobic or very small ligandsexamplessteroid hormones & thyroid hormones of
animalsNO (nitric oxide), a gas
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Turning on Genes
special proteins called transcription factors control which genes are turned on
example:Testosterone (steroid hormone) its activated receptor acts as
transcription factor that turns on specific genes
thus activated receptor carries out transduction of the signal
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TRANSDUCTION
when receptors for signaling molecules are membrane proteins the transduction stage is multistep pathway
usually involves inactive/active state by adding/removing phosphate group
benefit of multistep pathway is that possibility of amplification of signal if each step on pathway can transmit signal
to several molecules end up with large # activated molecules @ end of pathway
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Signal Transduction Pathway
in most cases original signaling molecule does not enter cell & is not passed along signaling pathway
1st step triggered by signaling molecule binding to receptor
proteins often used as relay molecules (protein interaction a unifying theme of all cellular regulation)
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Protein Phosphorylation & Dephosphorylation
protein kinase: enzyme that transfers phosphate groups from ATP protein most act on proteins different than
themselves most act on a.a. serine or threonine
(not tyrosine as in previous example) includes kinases in plants, animals, &
fungi many relay molecules in pathway are
kinases
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Phosphorylation Cascade
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Protein Phosphatases
enzymes that can rapidly remove phosphate groups from proteins (inactivating them)
also make kinases available to reuse
this phosphorylation/dephosphorylation system acts as molecular “switch” in cell “position of the switch” @ any given time depends on balance between active kinase & active phosphatase molecules
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Second Messengers
many signaling pathways involve small, nonprotein, water-soluble molecules or ions known as 2nd messengers
1st messenger is extracellular signaling molecule
2 most widely used 2nd messengers are cAMP & Ca++
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Cyclic AMP
epinephrine causes glycogen in hepatocytes to glucose w/out entering cells
search for 2nd messenger that transmits signal from plasma membrane metabolic pathway in cytoplasm
epinephrine binding to receptor followed by elevation of cytosolic concentrations of cAMP
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cAMP
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ATP cAMP
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Adenylyl Cyclase
enzyme embedded in plasma membraneATP cAMP in response to extracellular
signals directly or indirectly(epinephrine one of many)
indirectly: receptor protein changes when signaling molecule attaches activates many adenylyl cyclase possibly thru GTP
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GTP
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cAMP as 2nd Messenger
1st messenger activates G protein-coup-led receptor adenylyl cyclase ATP to cAMP activates another protein (usually protein kinase A)
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Protein Kinase A
serine/threonine kinaseonce activated it will phosphorylate other
proteins (depends on cell type)
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Other Regulation Mechanisms
G protein systems inhibit adenylyl cyclase
uses different signaling molecule & receptor
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understanding role of cAMP helps to explain how certain microbes cause disease
Vibrio cholerae: causes cholera in contaminated water forms biofilm over small intestines produces a toxin: enzyme that chemically
modifies a G protein involved in regulation of water & salt secretion (GTP --/ GDP so protein stays stuck in active form) high [cAMP] cells secrete large amts salts followed by water (osmosis)
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Vibrio cholerae
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Calcium Ions
many signaling molecules induce responses in target cell using signal transduction pathways that increase intracellular [Ca++]
more widely used than cAMP as 2nd messenger
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Animal Cells Plant Cells
contractionsecretion cell division
pathway that leads to greening in response to light
Effects of Ca++
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Ca++ Concentration Gradient
normally, [Ca++] inside cell << than outside
(up to 10,000x higher in extracellular fluid)
pumps used to send Ca++ into SER in muscle fibers (also in mitochondria, chloroplasts)
pathway leading to release of Ca++ from SER involves the 2nd messengers:
1. IP3 (inositol triphosphate)2. DAG (diacylglycerol)
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Ca++ Pathway in Tear Production
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RESPONSE
can be either nuclear or cytoplasmic responses
in nuclear responses the last kinase enters nucleus activates gene-regulating protein aka a transcription factor gene(s) transcribed mRNA …..
or transcription factor can turn gene offTranscription factors can regulate
several different genes
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Nuclear Response thru signal reception transduction (phosphorylation cascade)
gene activation
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Cytoplasmic Response
signaling pathway may regulate activity of a pathway (not synthesis of a protein)
open/close ion channelchange cell metabolism by controlling
enzymesregulate cell activities (yeast build
projections toward cell of opposite mating type)
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Yeast Reproduction
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How do signals induce directional cell growth during mating in yeast?
1. mating factor activates receptor2. G protein binds GTP & becomes
activated3. phosphorylation cascade activates Fus3
which then moves to plasma membrane4. Fus3 (a kinase) phosphorylates formin
this activating it5. formin initiates growth of
microfilamentsw that form shmoo projections
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Controlling Response
generally, response controlled @ >1 site (not just either “on” or “off”)
4 aspects of fine-tuning response:1. Signal amplification2. Specificity3. Efficiency4. Termination of signal
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Signal Amplification
enzyme cascades amplify the cell’s response to a signal
@ each step the # of activated products much > in preceding step of cascade
amplification happens because activated protein kinase stays in activated form long enuf to process numerous molecules of substrate
as result a small # signal molecules (like epinephrine) can release 100’s of millions of final product (glucose molecules)
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Specificity of Cell Signaling & Coordination of the Response
certain cells respond to some signals & have no response to others
2 different cells may have different responses to same signal
different kinds of cells turn on different genes so different kinds of cells have different collections of proteins
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What controls responses in cells?
response of a particular cell to a signal depends on its particular collection o
1. signal receptor proteins2. relay proteins3. proteins necessary to carry out the
response
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Signaling Efficiency: Scaffolding Proteins & Signaling Complexes
Scaffolding Proteins: type of large relay protein to which several other relay proteins are simultaneously attached increasing the efficiency of signal transduction
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Scaffolding Proteins Respond to same Signal
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Scaffolding Proteins
some are permanently held together (terminal axons in neurons)
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Relay Proteins that are Branch Points
Wiskott-Aldrich Syndrome (WAS) defect in single relay protein leads to:
abnl bleedingeczemapredisposition to:
infections leukemia
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Termination of the Signal
ability of cell to respond to new signals depends on reversibility of changes produced by prior signals
binding of signal molecules to receptors is reversible as [signal molecules] decreases fewer
receptor sites occupied by signal those unoccupied: receptor molecule reverts
to its inactive form
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Termination of Signal
any particular cell response occurs only when concentration of occupied receptors has reached a certain threshold:
if below threshold the cell response stops relay molecules return to inactive form cAMP AMP phosphorylated kinases lose phosphate
group
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Apoptosis integrates multiple cell-signaling pathways
apoptosis: programmed cell deathSteps:1. DNA gets copped up into pieces2. organelles & other cytoplasmic
components fragment 3. cell‘s parts put into vesicles which are
engulfed by phagocyctic cells4. “blebbing” occurs (cell becomes
multilobed)
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Apoptosis in Soil Worm C. elegans
2 genes identified Ced4 & Ced3 (ced for cell death)
both encode for proteins essential for cell death
are always present in a cell in inactive form
C. elegans has protein in outer mitochondrial membrane called Ced9 (from gene of same name) which serves as master regulator of apoptosis (has its brake on until “death signal” overrides it)
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Signals that Trigger Apoptotic Pathways
capase: group of proteins that mediate apoptosis
several different pathways involving 15 capases identified in mammals
which pathway used depends on type of cell & signal used
1 major pathway involves mitochondrial proteins that form pores in mitochondrial membrane releasing mitochondrial proteins, including cytochrome c, activate capases
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