2Evolution of cell signaling Similarities in pathways in bacteria, protists, fungi, plants, and animals suggest an early evolution of signaling pathways
3Bacteria communication “bacteria talking to each other” Quorum sensing- concentration of signaling molecules allows bacteria to sense their local densityEx- Vibrio – glowing bacteria (luciferase enzyme) give off auto inducers into their environment
5Quorum sensing can lead to the formation of biofilms
6Slime molds – chemical signaling Slime molds live as solitary amoebae.When slime mold cells begin to starve or dehydrate, they release a pheromone-like chemical called cyclic AMP. This messenger molecule alerts other slime mold amoebae. They detect the cAMP and follow the scent to join forces with the troubled amoebae forming a large mass of cells.Other slime mold amoebae detect the cAMP and follow the scent to join forces with the troubled amoebae.
7cAMP is an important chemical word in the language of cells and seems to be understood and made by all cells, even our own.
8Fruiting body formation in fungi chemical signaling
9Local and long-distance signaling Direct cytoplasmic connections: - gap junctions or plasmodesmata in plant cells - contact of surface molecules (cell-to- cell recognition via receptors
18Plasma membrane 1 Reception Transduction Receptor Signaling molecule 1 FigEXTRACELLULARFLUIDCYTOPLASMPlasma membrane11Reception2TransductionReceptorRelay molecules in a signal transduction pathwayFigure 11.6 Overview of cell signalingSignalingmolecule
19Plasma membrane 1 Reception Transduction Response Receptor Activation FigEXTRACELLULARFLUIDCYTOPLASMPlasma membrane1Reception2Transduction3ResponseReceptorActivationof cellularresponseRelay molecules in a signal transduction pathwayFigure 11.6 Overview of cell signalingSignalingmolecule
20ReceptionLigand – the signal molecule, fits like a lock and key to receptorMost ligands bind to cell surface receptors; some bind to intracellular receptorsUsually induces a shape change in receptor protein’s shape
21Types of receptors Bind with water-soluble molecules on membrane: G-Protein-linked ReceptorTyrosine Kinase ReceptorLigand-gated Ion ChannelBind with hydrophobic receptors:Intracellular Receptors
22G- Protein-Linked Receptors 7 protein helices that span the membraneBinding of the ligand to the G-protein receptor, activates a specific G protein located on the cytoplasm side. How - GDP becomes GTP.The activated G-protein activates a membrane-bound enzyme which continues on its pathway.The GTP goes back to GDP.Animation: Membrane-Bound Receptors that Activate G Proteins
23Signaling-molecule binding site Fig. 11-7aSignaling-molecule binding siteFigure 11.7 Membrane receptors—G protein-coupled receptors, part 1Segment thatinteracts withG proteinsG protein-coupled receptor
25How important is the G-protein system? Used by hormones, neurotransmitters, sensory reception, development….Many bacteria produce toxins that interfere with with G-protein systemsUp to 60% of medicines influence G-protein pathways
26Tyrosine kinase receptors Receptor tyrosine kinases are membrane receptors that attach phosphates from ATP to tyrosines (Remember kinase…ATP.)Once the receptors are activated, relay proteins bind to them and become activated themselves.A receptor tyrosine kinase can trigger multiple signal transduction pathways at once
28Tyrosine Kinase Receptors Binding of the signal molecules causes the two polypeptides to join.
29They are activated and act as enzymes to phosphorylate the tyrosines in the tails.
30The receptor protein is now recognized by relay proteins, triggering different effects.
31Ligand-gated ion channel A ligand-gated ion channel receptor acts as a gateWhen 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 receptorEx- in neurotransmitters and nervous signal transmission
34Intracellular Receptors Some receptor proteins are intracellular, found in the cytosol or nucleus of target cellsSmall or hydrophobic chemical messengers can readily cross the membrane and activate receptorsExamples of hydrophobic messengers are the steroid and thyroid hormones of animalsAn activated hormone-receptor complex can act as a transcription factor, turning on specific genes
35Hormone (testosterone) Plasma membrane Receptor protein Hormone- FigHormone(testosterone)EXTRACELLULARFLUIDPlasmamembraneReceptorproteinHormone-receptorcomplexDNAFigure 11.8 Steroid hormone interacting with an intracellular receptormRNANUCLEUSNew proteinCYTOPLASM
37Signal Transduction Allow for amplification of signals Signal coordination and regulationInvolves1) second messengers (cAMP and Ca+2)2) relay proteins such as protein kinases
38How does epinephrine work?...an example of cAMP messenging
39Epinephrine acts via cyclic AMP (cAMP) as a second messenger. An activated G protein activates the enzyme adenylyl cyclase (THINK CYCLING!) which turns ATP to cAMP.Then cAMP can activate other inactive molecules to reach the desired product.action of epinephrine Video | DnaTube.com - Scientific Video Site
41First messenger Adenylyl cyclase G protein GTP G protein-coupled FigFirst messengerAdenylylcyclaseG proteinG protein-coupledreceptorGTPATPSecondmessengercAMPFigure cAMP as second messenger in a G-protein-signaling pathwayProteinkinase ACellular responses
42cAMP second messenger systems Membrane Structure
43Calcium ions also act as second messengers. One example is activating an enzyme phospholipase C to produce two more messengers which will open Ca channels.The signal receptor may be a G protein or a tyrosine kinase receptor.
44EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein FigEXTRA-CELLULARFLUIDSignaling molecule(first messenger)G proteinDAGGTPG protein-coupledreceptorPIP2Phospholipase CIP3(second messenger)IP3-gatedcalcium channelFigure Calcium and IP3 in signaling pathwaysEndoplasmicreticulum (ER)VariousproteinsactivatedCellularresponsesCa2+Ca2+(secondmessenger)CYTOSOL
45RELAY PROTEINSEnzymes called protein kinases are also important links in transduction.A protein kinase catalyzes the transfer of PHOSPHATE GROUPS from ATP to another protein to activate it.Amplification is possible in these type of pathways.
48Cell Responses Alteration of metabolism Rearrangement of cytoskeleton Modulation of gene activity
49Modulating Gene Activity Growth factor Reception Receptor FigGrowth factorReceptionReceptorModulatingGeneActivityPhosphorylationcascadeTransductionCYTOPLASMInactivetranscriptionfactorActivetranscriptionfactorFigure Nuclear responses to a signal: the activation of a specific gene by a growth factorResponsePDNAGeneNUCLEUSmRNA
50Alteration of Metabolism Reception Transduction Inactive G protein FigReceptionBinding of epinephrine to G protein-coupled receptor (1 molecule)TransductionInactive G proteinActive G protein (102 molecules)Alteration ofMetabolismInactive adenylyl cyclaseActive adenylyl cyclase (102)ATPCyclic AMP (104)Inactive protein kinase AActive protein kinase A (104)Figure Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrineInactive phosphorylase kinaseActive phosphorylase kinase (105)Inactive glycogen phosphorylaseActive glycogen phosphorylase (106)ResponseGlycogenGlucose-1-phosphate(108 molecules)
51Rearrangement Of cytoskeleton RESULTS CONCLUSION FigRESULTSRearrangementOf cytoskeletonWild-type (shmoos)∆Fus3∆forminCONCLUSIONMatingfactor1Shmoo projection formingG protein-coupledreceptorForminPFus3ActinsubunitFigure How do signals induce directional cell growth in yeast?GTPPGDP2Phosphory-lationcascadeForminForminP4MicrofilamentFus3Fus3P53
53The Specificity of Cell Signaling and Coordination of the Response Different kinds of cells have different collections of proteins which allow cells to detect and respond to different signals.Even the same signal can have different effects in cells with different proteins and pathways
54FigSignalingmoleculeSame signal - different effects in cells with different proteins and pathwaysReceptorRelaymoleculesResponse 1Response 2Response 3Cell A. Pathway leadsto a single response.Cell B. Pathway branches,leading to two responses.Pathway branching and “cross-talk” further help the cell coordinate incoming signalsFigure The specificity of cell signalingActivationor inhibitionResponse 4Response 5Cell C. Cross-talk occursbetween two pathways.Cell D. Different receptorleads to a different response.
55Signaling Efficiency: Scaffolding Proteins and Signaling Complexes Scaffolding proteins are large relay proteins to which other relay proteins are attachedScaffolding proteins can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway
56Signaling Plasma molecule membrane Receptor Three different protein FigSignalingmoleculePlasmamembraneReceptorThreedifferentproteinkinasesFigure A scaffolding proteinScaffoldingprotein
57Apoptosis is programmed or controlled cell suicide Apoptosis (programmed cell death) integrates multiple cell-signaling pathwaysApoptosis is programmed or controlled cell suicideA cell is chopped and packaged into vesicles that are digested by scavenger cellsApoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cellsApoptosis is important in shaping an organism during embryonic development
58Ced-9 (inactive) Cell forms blebs Death- signaling molecule Active Fig bCed-9(inactive)CellformsblebsDeath-signalingmoleculeActiveCed-4ActiveCed-3OtherproteasesNucleasesFigure Molecular basis of apoptosis in C. elegansActivationcascade(b) Death signal