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Transcript
Cell-Cell Communication Overview: Cellular Signaling • Cells communicate with each other via chemical signals. • For example, the fight-or-flight response is triggered by a signaling molecule called epinephrine • Cell-to-cell communication is essential for both multicellular and unicellular organisms • Biologists have discovered some universal mechanisms of cellular communication © 2011 Pearson Education, Inc. Cell Signaling by Multicellular Organisms • Coordinates activities within individual cells to support the function of the organism as a whole • Examples: – Response to DNA damage • Could lead to expression of mutant proteins and cellular dysfunction and/or cancer if unchecked • Cell signaling pathways prevent this by activating DNA repair enzymes or initiating programmed cell death (apoptosis) © 2011 Pearson Education, Inc. Local Signaling • In local signaling, cells within multicellular organisms may communicate by: – contact through the cytoplasm of adjacent cells • cell junctions – cell-cell contact • Ligand on one cell binds to a receptor on an adjacent cell – short range signals • Cell secretes a soluble ligand that binds to a receptor on a nearby cell © 2011 Pearson Education, Inc. Local Signaling: Cytoplasmic contact at cell junctions Cell-cell contact between adjacent cells involving membrane bound ligands Short range signals involving soluble ligands Local signaling Electrical signal along nerve cell triggers release of neurotransmitter. Target cell Secreting cell Local regulator diffuses through extracellular fluid. (a) Paracrine signaling Neurotransmitter diffuses across synapse. Secretory vesicle Target cell is stimulated. (b) Synaptic signaling Long-Distance Signaling • In long distance signaling, cells within multicellular organisms may communicate use chemicals called hormones – synthesized by cells in one region of the body – travel through the bloodstream to reach their cellular targets in other regions of the body © 2011 Pearson Education, Inc. Figure 11.5b Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream. Target cell specifically binds hormone. (c) Endocrine (hormonal) signaling Signal Specificity and Cell Specialization • Only the signaling molecule that fits the shape of a specific receptor can trigger a response in a cell • Mediated by shape and chemical nature of interacting regions • Different cell types produce different receptors • A cell synthesizes many different kinds of receptors, depending on conditions or stages in its life cycle • The same signal can have different meanings for various target cells © 2011 Pearson Education, Inc. The Three Stages of Cell Signaling: (within 1 cell) 1) Reception 2) Transduction 3) Response © 2011 Pearson Education, Inc. Figure 11.6-1 EXTRACELLULAR FLUID 1 Reception Receptor Signaling molecule CYTOPLASM Plasma membrane Figure 11.6-2 EXTRACELLULAR FLUID 1 Reception CYTOPLASM Plasma membrane 2 Transduction Receptor Relay molecules in a signal transduction pathway Signaling molecule Figure 11.6-3 EXTRACELLULAR FLUID 1 Reception CYTOPLASM Plasma membrane 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signaling molecule Step 1: Signal Reception • A signaling molecule binds to a receptor protein, causing it to change shape, and initiating the transduction of the signal • Most receptors are plasma membrane proteins but some are inside of the cell (cytoplasmic/nuclear receptors) • The binding between a signal molecule (ligand) and receptor is highly specific © 2011 Pearson Education, Inc. Cell Surface and Intracellular Receptors Receptors in the Plasma Membrane • There are three main types of membrane receptors – Ion channel receptors – G protein-coupled (linked) receptors – Protein kinase receptors (aka receptor tyrosine kinases) © 2011 Pearson Education, Inc. Ligand-Gated Ion Channel Receptors • A ligand-gated ion channel receptor acts as a gate • When a ligand binds to the receptor, the shape changes, allowing specific ions, such as Na+ or Ca2+, to pass into the cell through a channel in the receptor © 2011 Pearson Education, Inc. Ligand-Gated Ion Channel Receptors Signaling molecule Na+ Extracellular fluid Receptor Cytosol 1 Ion channel is closed. 2 When signaling molecule binds to receptor, the channel changes shape and opens. Sodium ions enter the cell. Fig. 6-5a, p. 140 G Protein Linked Receptors • A GPCR is a plasma membrane receptor that works with the help of a G protein, located in the cytoplasm • Upon ligand binding the G protein is turned on by the exchange of GDP for GTP • The G protein then helps to transmit the intracellular signal © 2011 Pearson Education, Inc. G Protein Coupled Receptors Signaling molecule Receptor G protein Enzyme Cytosol GDP 1 Inactive state: the three subunits of G protein are joined and it is bound to GDP GTP 2 Ligand binding: receptor binds to G protein causing GDP to be replaced with GTP and the separation of one subunit. This is the active state. Fig. 6-5b, p. 140 Protein Kinase Receptors • PKRs are membrane receptors that also have enzymatic activity • transfer phosphate groups (phosphorylation) from ATP to specific tyrosine residues on proteins • A receptor tyrosine kinase can trigger multiple signal transduction pathways at once • Abnormal functioning of PKRs is associated with many types of cancers © 2011 Pearson Education, Inc. Receptor Tyrosine Kinases Signaling molecule (ligand) Ligand-binding site helix in the membrane Signaling molecule Tyrosines CYTOPLASM Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins (inactive monomers) 1 Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Dimer 2 Activated relay proteins 3 Tyr Tyr P Tyr Tyr P P Tyr Tyr P Tyr Tyr P Tyr Tyr P P Tyr Tyr P Tyr Tyr P Tyr Tyr P P Tyr Tyr P 6 ATP Activated tyrosine kinase regions (unphosphorylated dimer) 6 ADP Fully activated receptor tyrosine kinase (phosphorylated dimer) 4 Inactive relay proteins Cellular response 1 Cellular response 2 Intracellular Receptors • Intracellular receptors are found in the cytosol or nucleus – most are transcription factors that regulate expression of specific genes • Signaling molecules are small, hydrophobic molecules that diffuse across the membranes of target cells – Some combine with receptors in the cytosol, then move into the nucleus (e.g. steroid hormones) – Some bind to receptors already bound to DNA inside the nucleus (e.g. thyroid hormones) © 2011 Pearson Education, Inc. Hormone (testosterone) Steroid hormone interacting with an intracellular receptor EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA mRNA NUCLEUS CYTOPLASM New protein Step 2: Signal Transduction • Cascades of molecular interactions relay signals from receptors to target molecules in the cell. • Signals are relayed by: – Protein kinases – Second messengers • Both of these mechanisms help to amplify the signal inside of the cell © 2011 Pearson Education, Inc. Step 2: Signal Transduction • Protein kinases help to transmit signals through a cascade of protein phosphorylations – Protein kinases transfer phosphate groups from ATP to other proteins, a process called phosphorylation • acts like a molecular on-off switch – The addition of phosphate groups (by kinases)acts like an “on” switch and activates proteins – The removal of phosphate groups (by phosphatases) acts like an “off” switch and deactivates proteins © 2011 Pearson Education, Inc. Figure 11.10 Signaling molecule Receptor Signal transduction by protein kinases involving a phosphorylation cascade Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP P Active protein kinase 2 PP Pi Inactive protein kinase 3 ATP ADP Pi Active protein kinase 3 PP Inactive protein P ATP P ADP PP Pi Active protein Cellular response Step 2: Signal Transduction • Second messengers – Ions or small molecules that amplify signals inside the cell and relay them to other signaling or target proteins – Ex: cyclic AMP (cAMP), inositol triphosphate (IP3) , and calcium ions (Ca2+) © 2011 Pearson Education, Inc. 1 Ligand binds to Signaling molecule Extracellular fluid GPCR, activating (first messenger) Adenylyl the G protein cyclase Receptor G protein and causing one subunit to bind to and activate Plasma Adenylyl membrane Cyclase, which then catalyzes Cytosol formation of cAMP from ATP cAMP 2 Signal is amplified and relayed by the second messenger cAMP 3 Response: some cell process is altered cAMP cAMP cAMP Protein Protein Protein Alters metabolism Affects gene activity Second messenger Opens or closes ion channels Fig. 6-7, p. 143 Figure 11.14-3 EXTRACELLULAR FLUID Signaling pathway involving the second messengers 2 IP and Ca 3 G protein Signaling molecule (first messenger) DAG GTP G protein-coupled receptor Phospholipase C PIP2 IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Various proteins activated Ca2 Ca2 (second messenger) Cellular responses Signal Amplification • Enzyme cascades amplify the cell’s response • At each step, the number of activated products is much greater than in the preceding step © 2011 Pearson Education, Inc. Signal Amplification Step 3: Response Cell signaling leads to regulation of cellular activity including: •Opening or closing of ion channels •Alteration of enzyme activity, leading to metabolic changes • Ex, fight or flight response •Alteration of specific gene activity • specific proteins made or not made in response •Apoptosis © 2011 Pearson Education, Inc. Cellular Response to Signaling Growth factor Reception Receptor Cellular Response: Activation of a specific gene by a growth factor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor P Response DNA Gene NUCLEUS mRNA Termination of the Signal • Inactivation mechanisms are an essential aspect of cell signaling • If ligand concentration falls, fewer receptors will be bound • Unbound receptors revert to an inactive state © 2011 Pearson Education, Inc. How does cell signaling trigger the desperate flight of this gazelle? Link Fight or Flight Signaling Pathway • Epinephrine (adrenaline), a hormone, is released by the adrenal gland. • It travels through the blood stream to reach its target in muscle or liver cells. • There is binds to a G protein coupled receptor and initiates a signaling cascade • Results in glucose release by the cells leading to increased heart and breathing rate Fight or Flight Signaling Pathway Epinephrine G protein coupled receptor G protein Extracellular fluid Adenylyl cyclase Plasma membrane Cytosol 1 Reception of Signal Fig. 6-9a, p. 144 Fight or Flight Signaling Pathway Epinephrine G protein coupled receptor G protein separates Adenylyl cyclase 2 Initiation of Signal Transduction Fig. 6-9b, p. 144 Ligand: epinephrine G protein coupled Receptor Adenylyl cyclase activated Dissociation of activated G protein Phosphorylated Protein kinase A Fight or Flight Protein Phosphorylated protein (active) Signaling Pathway Glycogen is broken down into 3 Cellular Response Animation glucose, which is released by the cell. Causes increased blood flow and heart rate as well as increased breathing rate. Fig. 6-9c, p. 144 Apoptosis integrates multiple cell-signaling pathways • Apoptosis is programmed or controlled cell suicide • Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells • Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells © 2011 Pearson Education, Inc. Role of Apoptosis in Development and Disease • Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals • Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers © 2011 Pearson Education, Inc. Figure 11.22 Role of Apoptosis in Development Interdigital tissue Cells undergoing apoptosis Space between 1 mm digits Evolutionary History of Cell Signaling • Similarities in cell communication among diverse organisms suggest that the molecules and mechanisms used in information transfer evolved long ago • Evidence suggests that cell communication first evolved in prokaryotes – Some signal transduction pathways found in organisms as diverse as yeasts and animals are quite similar – Highly conserved nature suggests an evolutionary relationship Cellular Signaling and Development • Cellular signaling plays a critical role in development and maintenance of multicellular organisms – establishment of body axes – cell fate decisions leading to the formation of germ layers and organ development – maintenance of stem cells within the body Cellular Signaling and Disease • Mutations that cause over- or underactive cell signaling can result in disease – diabetes, neurological diseases, autoimmune diseases, cancer • Many therapeutic drugs seek to block or balance out over- or underactive signaling pathways – birth control, antihistamines, anti-psychotics, anti-cancer drugs Cellular Signaling and Biotechnology • Understanding these pathways allows scientists to modify or manipulate biological systems and cellular physiology – – – – Drugs to treat disease Control of fruit ripening Use of growth hormones in poultry, etc Doping by athletes (EPO, HGH) Helpful Videos/Animations: • AP Biology Hayescience “Cell Communication” a general overview- can go back to look at specifics https://www.youtube.com/watch?v=XtN9YjIJhz8 • Crash Course “Nervous System Part 3: Synapses” a general overview https://www.youtube.com/watch?v=VitFvNvRIIY • Bozeman “Cell Communication” https://www.youtube.com/watch?v=xnGXItWrJ3k • Bozeman “Signal Transduction Pathways” https://www.youtube.com/watch?v=qOVkedxDqQo • Life (your textbook): Ch. 7 animations - “Signal Transduction Pathway” & “Signal Transduction & Cancer” http://bcs.whfreeman.com/thelifewire9e/default.asp#542578__591101__ • The Penguin Prof “Signal Transduction” https://www.youtube.com/watch?v=pH_ibPHK0y0 • Learn Genetics “Fight or Flight Response” example of Signal Transduction http://learn.genetics.utah.edu/content/cells/cellcom/ SEE ALSO THE CELL SIGNALING WEBQUEST ACTIVITY FOR ADDITIONAL SPECIFIC SUPPORT VIDEOS/ANIMATIONS. Cell Signaling by Single Celled Organisms • Influences how they respond to the environment • Examples: – Quorum sensing in bacteria • Send and receive signaling relaying info on population density • When few organisms present little signaling • As numbers increase, more signaling, which can result in different cellular outcomes © 2011 Pearson Education, Inc. Cell Signaling by Single Celled Organisms – Quorum sensing in bacteria • Pseudomonas aerginosa live in host without harm until reach a certain population density • At high density they form a biofilm and cell signaling changes their gene expression to start producing toxins – Biofilm: A community of microorganisms attached to a solid surface; requires the coordinated activity of numerous bacteria • Results in host pathology © 2011 Pearson Education, Inc. Cell Signaling by Single Celled Organisms – Quorum sensing in Pseudomonas aerginosa © 2011 Pearson Education, Inc. Cell Signaling by Single Celled Organisms – Quorum sensing in bacteria • Vibrio fischeri is a bioluminescent bacteria that lives in a mutualistic relationship within the light producing organ of a Hawaiian squid • In low numbers and with low signaling, bacteria do not synthesize the light producing protein • In high numbers and with high signaling, bacteria do synthesize the light producing protein © 2011 Pearson Education, Inc. Cell Signaling by Single Celled Organisms – Quorum sensing in Vibrio fischeri © 2011 Pearson Education, Inc.