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Cell Signaling & Communication. Cellular Signaling. cells respond to various types of signals signals provide information about a cell’s environment. gaseous hydrocarbon. signal molecules are chemically diverse. steroid. catecholamine. peptide. Signal Receptors.
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Cellular Signaling • cells respond to various types of signals • signals provide information about a cell’s environment
gaseous hydrocarbon signal molecules are chemically diverse steroid catecholamine peptide
Signal Receptors • cells respond to signals only if they have the right signal receptors • receptors bind or absorb specific signals • cells without appropriate receptors “ignore” specific signals
some signals communicate local information some signals communicate over long distanceFigure 15.1
Cell Responses • signaling evokes specific responses from specific cells • a signal does not specify a cell’s response • a cell’s response is determined by the cell
Cell Responses • The “Fight or Flight” Response • epinephrine (adrenaline) is released into the blood stream • receptors in different tissues bind epinephrine • heart: beats faster, more strongly • digestive system: blood vessels constrict • liver: cleave glycogen; release glucose • adipose tissue: breaks down triglycerides
Cell Responses • cell responses involve three components • receptor • transduction mechanism (amplifier) • effect
change in the environment signal: solute in intermembrane spacereceptor: EnvZFigure 15.2 transduction: >autophosphorylate EnvZ >phosphorylate OmpR, >activate OmpC amplification: one gene, many proteinseffect: block pores
Receptors • each cell makes a specific group of receptors so it can respond to a specific set of signals • many in the plasma membrane • some in the cytoplasm or the nucleoplasm • a receptor has a binding site for its ligand, the signal molecule • ligand binding causes a conformational change in the receptor
Figure 15.3 Human growth hormone Human growth Hormone receptor
ligand binding causes a conformational change in the receptorFigure 15.4
Receptors • different types of receptors react to signals differently • gated ion channels • regulate passage of Na+, K+ Ca2+, Cl- • ligand binding causes the channel to open
Receptors • different classes of receptors react to signals differently • receptor protein kinases • ligand binding activates a cytoplasmic kinase domain • dimerizaton often occurs • autophosphorylation further activates the receptor • phosphorylation of cellular targets begins signal transduction
Receptors • different classes of receptors react to signals differently • G protein-linked receptors • ligand binding causes the receptor to bind an inactive G protein-GDP • G protein is activated to G protein-GTP • GTP-bearing subunit diffuses to effector • effector initiates cell response • G protein may activate or inhibit effector
Receptors • different classes of receptors react to signals differently • cytoplasmic receptors bind nonpolar ligands • ligand binding lets the receptor enter the nucleus & activate transcription • nuclear receptors bind ligands in the nucleus • receptors without bound ligands repress transcription • ligand binding activates transcription
Transducers • signal transduction • converting the information “signal X has arrived” into a cellular response • may be “direct” by the activated receptor • may be “indirect” by a second messenger • enzymatic steps in signal transduction pathways amplify signal strength
transduction of a growth factor signal amplifies the signal at several stepsFigure 15.9
Transducers • second messengers can trigger multiple responses one signal • cAMP • synthesized by a G protein-activated membrane-bound adenylyl cyclase • binds to ion channels in some cells • binds to protein kinases in other cells • may do both in some cells
Transducers • second messengers can trigger multiple responses one signal • receptoractivatesG proteinactivates effector, phospholipase C • phospholipase C cleaves PTI into inositol triphosphate (IP3) and diacylglycerol (DAG) • DAG activates a membrane-bound, Ca2+-dependent protein kinase C (PKC) • IP3opens a Ca2+ channel in ER membrane • Ca2+activates PKC • PKC phosphorylates many cellular target molecules
phosphatidyl inositol bisphosphatephospholipase CIP3 + DAG DAG glycerol phosphate IP3
Transducers • second messengers can trigger multiple responses one signal • Ca2+ is a common second messenger • a steep Ca2+ gradient exists across ER & plasma membranes • opening gated Ca2+ channels raises cytoplasmic [Ca2+] • Ca2+ activates many cellular targets • Ca2+ activation often involves calmodulin
Transducers • second messengers can trigger multiple responses one signal • nitric oxide (NO) is a gas • NO synthase is activated by Ca2+ in response to IP3 after an acetylcholine receptor binds its ligand • NO diffuses to a neighboring smooth muscle cell and activates an enzyme causing relaxation
smooth muscle relaxation response to acetylcholine signaRelax!!Figure 15.13
Regulation of Signal Transduction • activation of signal transduction is opposed by inactivating factors • NO breaks down very rapidly • Ca2+ channels open very briefly & Ca2+ pumps remove Ca2+ immediately • protein phophatases inactivate P-enzymes • GTPases return G proteins to inactive form • cAMP is converted to AMP • members of different types of pathways interact in regulatory roles
Effects • cell responses include • opening membrane channels • important in sensory cells • odorant receptors send nerve impulses to the brain
activated G protein activates adenylyl cyclase 1. odorant receptors are displayed on the surface of nasal epithelial cells; 2. each receptor binds a particular odorant molecule;3. odorant binding activates a G proteinFigure 15.14 cAMP opens ion channels to signal the brain
Effects • cell responses include • opening of membrane channels • alteration of enzyme activities • covalent modification (phosphorylation) or allosteric modification (cAMP) cause expose active sites • glycogen metabolism in the liver is regulated by a protein kinase cascade in response to epinephrine
epinephrine causes glucose release from glycogenstores in the liverFigure 15.15
Effects • cell responses include • opening of membrane channels • alteration of enzyme activities • changes in gene transcription • a common response is new protein synthesis • the Ras pathway stimulates cell division in response to growth factors
Direct Intercellular Communication • animal cells communicate directly, through gap junctions • small molecules diffuse between cells • ATP • second messengers • waste or nutrient molecules • tissue function can be coordinated
gap junctions between adjacent animal cells allow direct communicationFigure 15.16 ~ 1 nm
Direct Intercellular Communication • plant cells communicate through plasmodesmata • lined by plasma membrane • occupied by desmotubules • permit rapid exchange of small molecules