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Transcript
Cell Communication 1.Cells need to communicate 2. Cells have several mechanisms for communicating We are going to learn about several of these mechanisms! Local Signaling (short distances) • Cells in a multicellular organisms communicate by chemical messengers • In local signaling, animal cells may communicate by direct contact • Animal and plant cells have cell junctions (remember; gap junctions and plasmodesmata) that directly connect the cytoplasm of adjacent cells LE 11-3 Plasma membranes Gap junctions between animal cells Cell junctions Cell-cell recognition Plasmodesmata between plant cells Local Signaling (short distances) – con’t • In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances Local signaling Target cell Secreting cell Local regulator diffuses through extracellular fluid Paracrine signaling Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Secretory vesicle Target cell is stimulated Synaptic signaling Long-Distance Signaling Long-distance signaling In long-distance signaling, plants and animals use chemicals called hormones Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell Hormonal signaling The Three Stages of Cell Signaling: A Preview • Earl W. Sutherland discovered how the hormone epinephrine acts on cells • Sutherland suggested that cells receiving signals went through three processes: – Reception – Transduction - conversion of signal to a form that can bring about a response – Response Reception • Signal molecule (ligand) binds to receptor – Highly specific – Conformational change in receptor often initiates transduction of the signal • Receptors found in two places – Intracellular receptors found inside the cell (in cytoplasm or nucleus) – Plasma membrane receptors bind to water-soluble ligands Intracellular 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 genes LE 11-6 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex The steroid hormone testosterone passes through the plasma membrane. Testosterone binds to a receptor protein in the cytoplasm, activating it. The hormonereceptor complex enters the nucleus and binds to specific genes. DNA The bound protein stimulates the transcription of the gene into mRNA. mRNA NUCLEUS New protein The mRNA is translated into a specific protein. CYTOPLASM Receptors in the Plasma Membrane • 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-linked receptors – Receptor tyrosine kinases – Ion channel receptors • A G-protein-linked receptor is a plasma membrane receptor that works with the help of a G protein • The G-protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive • http://highered.mcgrawhill.com/sites/0072507470/student_view0/chapter1 7/animation__membranebound_receptors_that_activate_g_proteins.html • http://www.dnatube.com/video/4254/G-ProteinReceptor-Animation LE 11-7ab Plasma membrane G-protein-linked receptor Activated receptor Signal molecule GDP CYTOPLASM Enzyme G protein (inactive) GDP GTP Activated enzyme GTP GDP Pi Cellular response Inactive enzyme LE 11-7b Signal molecule Signal-binding site a Helix in the membrane Signal molecule Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins (inactive monomers) CYTOPLASM Dimer Activated relay proteins Tyr Tyr Tyr Tyr Tyr Tyr 6 ATP Activated tyrosinekinase regions (unphosphorylated dimer) 6 ADP P Tyr P Tyr P Tyr Tyr P P Tyr P Tyr Fully activated receptor tyrosine-kinase (phosphorylated dimer) P Tyr P Tyr P Tyr P Tyr P Tyr P Tyr Inactive relay proteins Cellular response 1 Cellular response 2 • Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines • A receptor tyrosine kinase can trigger multiple signal transduction pathways at once • http://faculty.plattsburgh.edu/donald.slish/tyrosinek inase/tk1.html • http://www.dnatube.com/video/4097/TK-ReceptorAnimation • http://www.dnatube.com/video/539/ReceptorTyrosine-Kinase-Activation-and-Signalling • An 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 receptor • http://highered.mcgrawhill.com/sites/0072495855/student_view0/chapter2/ani mation__receptors_linked_to_a_channel_protein.html LE 11-7c Signal molecule (ligand) Gate closed Ligand-gated ion channel receptor Ions Plasma membrane Gate open Cellular response Gate closed Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell • Transduction usually involves multiple steps • Multistep pathways can amplify a signal: A few molecules can produce a large cellular response • Multistep pathways provide more opportunities for coordination and regulation LE 11-5_2 EXTRACELLULAR FLUID CYTOPLASM Plasma membrane Reception Transduction Receptor Relay molecules in a signal transduction pathway Signal molecule Signal Transduction Pathways • The molecules that relay a signal from receptor to response are mostly proteins • Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated • At each step, the signal is transduced into a different form, usually a conformational change Protein Phosphorylation and Dephosphorylation • In many pathways, the signal is transmitted by a cascade of protein phosphorylations (adding of a phosphate) • Phosphatase enzymes remove the phosphates • This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off • Some pathways involve small, nonprotein watersoluble molecules or ions called second messengers (ex. Calcium ions & Cyclic AMP) Small Molecules and Ions as Second Messengers • Second messengers are small, nonprotein, watersoluble molecules or ions • The extracellular signal molecule that binds to the membrane is a pathway’s “first messenger” • Second messengers can readily spread throughout cells by diffusion • Second messengers participate in pathways initiated by G-protein-linked receptors and receptor tyrosine kinases Cyclic AMP • Cyclic AMP (cAMP) is one of the most widely used second messengers • Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal LE 11-9 Phosphodiesterase Adenylyl cyclase Pyrophosphate P ATP H2O Pi Cyclic AMP AMP • Many signal molecules trigger formation of cAMP • Other components of cAMP pathways are G proteins, G-protein-linked receptors, and protein kinases • cAMP usually activates protein kinase A, which phosphorylates various other proteins • Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase LE 11-10 First messenger (signal molecule such as epinephrine) Adenylyl cyclase G protein G-protein-linked receptor GTP ATP cAMP Second messenger Protein kinase A Cellular responses Calcium ions and Inositol Triphosphate (IP3) • Calcium ions (Ca2+) act as a second messenger in many pathways • Calcium is an important second messenger because cells can regulate its concentration LE 11-11 EXTRACELLULAR FLUID Plasma membrane Ca2+ pump ATP Mitochondrion Nucleus CYTOSOL Ca2+ pump Endoplasmic reticulum (ER) ATP Key Ca2+ pump High [Ca2+] Low [Ca2+] • A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol • Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as second messengers LE 11-12_1 EXTRACELLULAR Signal molecule FLUID (first messenger) G protein DAG GTP G-protein-linked receptor IP3-gated calcium channel Endoplasmic Ca2+ reticulum (ER) CYTOSOL Phospholipase C PIP2 IP3 (second messenger) LE 11-12_2 EXTRACELLULAR Signal molecule FLUID (first messenger) G protein DAG GTP G-protein-linked receptor Phospholipase C IP3 (second messenger) IP3-gated calcium channel Endoplasmic Ca2+ reticulum (ER) CYTOSOL PIP2 Ca2+ (second messenger) LE 11-12_3 EXTRACELLULAR Signal molecule FLUID (first messenger) G protein DAG GTP G-protein-linked receptor Phospholipase C PIP2 IP3 (second messenger) IP3-gated calcium channel Endoplasmic Ca2+ reticulum (ER) CYTOSOL Ca2+ (second messenger) Various proteins activated Cellular responses Response: Cell signaling leads to regulation of cytoplasmic activities or transcription • The cell’s response to an extracellular signal is sometimes called the “output response” • Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities • The response may occur in the cytoplasm or may involve action in the nucleus • Many pathways regulate the activity of enzymes LE 11-5_3 EXTRACELLULAR FLUID CYTOPLASM Plasma membrane Reception Transduction Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signal molecule Response • Cell signaling leads to regulation of transcription or cytoplasmic activities – Protein synthesis – Turn genes on or off – Transcription factors – May affect activity of enzymes – May cause cytoskeleton rearrangement LE 11-13 Reception Binding of epinephrine to G-protein-linked receptor (1 molecule) Transduction Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104) Inactive phosphorylase kinase Active phosphorylase kinase (105) Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Response Glycogen Glucose-1-phosphate (108 molecules) Termination of the Signal • Inactivation mechanisms are an essential aspect of cell signaling • When signal molecules leave the receptor, the receptor reverts to its inactive state