Cell communicationCell communicationCell communicationCell communicationThe Three Stages of Cell SignalingSlide 6Slide 7Slide 8Slide 9G protein-coupled receptorGPCR signalingReceptor tyrosine kinasesReceptor tyrosine kinasesActions of nerve growth factor receptor TrkALigand-gated ion channelsIntracellular ReceptorsIntracellular ReceptorsIntracellular ReceptorsTransduction: Intracellular signal transduction pathwaysProtein phosphorylationProtein phosphorylationIntracellular 2nd messengersCyclic AMPCyclic AMP effectorsCalcium as a 2nd messengerCalcium as a 2nd messengerCalcium as a 2nd messengerCalcium as a 2nd messengerCalcium as a 2nd messengerCell ResponseCell ResponseCell ResponseFine-Tuning of the ResponseSlide 34Slide 35Slide 36Signaling EfficiencyExample of need for efficiencyCell communicationExtracellularIntracellularIons, water, moleculesInformationControl of cell functionHow do cells communicate with one another, and how do the signals affect cell function?Cell communication•Cell-to-cell communication is essential for multicellular organismsThe combined effects of multiple signals determine cell response•Direct exchange of materials between the cytoplasm. Gap junctions and plasmodesmata•Direct interaction of cell surface moleculescell adhesion.Cell communication•Indirect communication between two non-contacting cells.A signal released from one cell that affects the function of a second•Different types of signaling depends on the distance that separates the 2 cell types.•In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distancesParacrine: act on other cellsAutocrine: act on itself or like cellsSignaling cellSignaling cellCell communication•In long-distance signaling, plants and animals use chemicals called hormones–EndocrineSignaling cellThe Three Stages of Cell Signaling•Cells receiving signals went through three processes:ReceptionTransductionResponse•Receptor specificitySignals (ligands) cannot alter cell function until they bind to a specific molecule - a receptor.This interaction can be very specific•Two major receptor types:Those located in the membrane that interact with hydrophilic signals that cannot cross the plasma membrane. •Amino acids, their derivatives, and peptides.Those found in the cytoplasm that bind to hydrophobic signals that can cross the plasma membrane. •Steroids.Reception1EXTRACELLULARFLUIDSignalingmoleculePlasma membraneCYTOPLASM1ReceptorLigand1EXTRACELLULARFLUIDSignalingmoleculePlasma membraneCYTOPLASMTransduction2Relay molecules in a signal transduction pathwayReception1ReceptorEXTRACELLULARFLUIDPlasma membraneCYTOPLASMReceptorSignalingmoleculeRelay molecules in a signal transduction pathwayActivationof cellularresponseTransduction Response23Reception11. Alteration of enzyme function2. Alteration of gene expressionReception: A signal molecule binds to a receptor protein, causing it to change shape•The binding between a signal molecule (ligand) and receptor is highly specificA shape change in a receptor is often the initial transduction of the signal•Most signal receptors are plasma membrane proteinsMost water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane•There are three main types of membrane receptors:G protein-coupled receptorsReceptor tyrosine kinasesIon channel receptorsG protein-coupled receptor •A G protein-coupled receptor (GPCR) is a plasma membrane receptor that works with the help of a G proteinAn intracellular guanine nucleotide binding protein.•GTP or GDPThe G protein acts as an on/off switch.•Inactive when GDP is bound•Active when GTP is bound•Largest family of cell surface receptors.5% of the genes in the nematode C. elegans.Over 1000 involved in the sense of smell alone.•Signaling molecules range from proteins to small peptides, amino acid derivatives, and fatty acids.•Despite their diversity, all have the same general structure.Span the membrane 7 times.Called serpentine receptors.GPCR signalingEffector proteinReceptor tyrosine kinases•Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosinesCan trigger multiple signal transduction pathways at once•To function they have two components:a kinase (which is actually part of the receptor itself)a target (or ‘relay’) protein, which is separate from the receptor•A functional receptor has two parts, which dimerize when the ligand binds. Dimerization activates the kinase part of receptor.Receptor tyrosine kinases•The kinase moves a phosphate group from ATP to a specific amino acid located within the cytoplasmic proteinTyrosine, serine, or threoninePhosphorylates itself or autophosphorylation•When phosphorylated they become active and activate relay proteins, again by phosphorylation.Actions of nerve growth factor receptor TrkALigand-gated ion channels•A ligand-gated ion channel receptor acts as a gate when the receptor changes shape•When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptorIntracellular Receptors•Some receptor proteins are intracellular, found in the cytosol or nucleus of target cells•Small or hydrophobic chemical messengers can readily cross the membrane and activate receptorsExamples of hydrophobic messengers are the steroid and thyroid hormones of animals•An activated hormone-receptor complex can act as a transcription factor, turning on specific genesIntracellular ReceptorsIntracellular ReceptorsTransduction: Intracellular signal transduction pathways•Signal transduction pathways are cascades of intracellular events. Triggered by the binding of the ligand to its specific receptor.•Signal transduction usually involves multiple stepsBenefits:•Can amplify a signal: A few molecules can produce a large cellular response•Provide more opportunities for coordination and regulation of the cellular responseThe molecules that relay a signal from receptor to response are mostly proteinsReceptor activates another protein, which activates another, and so onA cascadeProtein phosphorylation•At each step, the signal is transduced into a different form, usually a shape change in a proteinAddition of a phosphate will induce a conformational change.•Protein kinases transfer