Cell Communication PDF

Cell Communication Key Concepts: General Features of Cell Communication Cellular Receptors and Their Activation Signal Transduction and the Cellular Response Hormonal Signaling in Multicellular Organisms 1  Why do cells...

Cell Communication Key Concepts: General Features of Cell Communication Cellular Receptors and Their Activation Signal Transduction and the Cellular Response Hormonal Signaling in Multicellular Organisms 1  Why do cells need signals? 1 To respond to a changing environment A cellular response to the environment can be critical for survival Example: Glucose signals yeast cells to increase glucose transporters and enzymes allowing efficient uptake and use of glucose  A cellular response to changes in the environment can be critical for survival Glucos Yeast Glucose Glucose e faws of cell recepto transporte r r diffusion N more glucose transported in Loading… Exposure to glucose Metabolic enzyme Due to glucose in the environment, the yeast cell on the right has undergone a cellular response by synthesizing more glucose transporters and enzymes that are needed to metabolize glucose. 3  Why do cells need signals? Answer: To communicate with each other Cells in the growing shoot tip sense light and send a signal (auxin) to cells on the nonilluminated side of the shoot. Growing Cells located shoot below the tip of plant growing tip receive this signal and elongate, thereby Phototropism causing a bend in the shoot. In this way, the tip grows plants toward the light. allows bind to the cell ff light comm doesn't.to or always chemical have a (inset): © Robert J. Erwin/Photo Researchers, Inc. can be C Phototropism in plants allows multiple physical as cells to change shape, bending the plant in a coordinated way well. 4 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  a Receptor factor shmooing S 1 Exchange a of mating factors a factor Yeast cell, Yeast cell, mating type a mating type D Loading… a a 2 Mating result i 2 haploid a cells 3 New a/ O a/ a cell 2 haploid es cells What Do Cells Need To Communicate With Each Other? bacterias communicate through molecules 6 Cell Signalling Requirements Signaling molecule ------------------- Large hydrophilic molecules Small hydrophobic molecules Hormones Receptor -------------- Transmembrane Not metabolism Cytosolic only Nucleoplasm h ↳ to act as transcriptional activators going can effect transcription of genes) 7  Signals relayed between cells Signaling Gap Membrane-bound molecule junction signaling molecule Target cell Target Recepto cell r (a) Direct intercellular signaling: (b) Contact-dependent signaling: (c) Autocrine signaling: Cells Signals pass through a cell junction Membrane-bound signals bind release signals that affect from to themselves and nearby target the cytosol of one cell to adjacent cells. receptors on adjacent cells. cells. Direct intercellular signaling: Cell junctions allow signaling molecules to pass from one cell to another. Contact-dependent signaling: Molecules bound to the surface of cells serve as signals to cells coming in contact with them. Autocrine signaling: Cells secrete signaling molecules that bind to their own cell surface or similar neighboring cells. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 8  Signals relayed between cells Paracrine signaling Signal does not affect originating cell, but does influence nearby alls. Endocrine signaling ( Paracrine signaling: Cells release Signals called hormones travel signals that affect nearby target cells. long distances and are usually longer lessing in effect. receptor tells which als receive the hor. more a which don't. 9 Three stages of cell signaling Receptor activation Fill in the blank Signaling molecule binds to question receptor Signal transduction Activated receptor stimulates a sequence of changes a signal transduction pathway Cellular response side Different responses possible note Change enzyme activity [phosphorylations Change function of structural proteins 7 Change gene expression [ synthesis of enzymes]  Cell signaling: responding to the outside world Cells interact with their environment by interpreting extracellular signals via proteins that span their plasma membrane called receptors extracellular Receptors are comprised of -------------- and intracellular domains --------------------------------- extracellular domain The --------------------------------relays information about the outside world to the intracellular domain intracellular domain Loading… The --------------------------then interacts with other intracellular signaling proteins intracellular signaling proteins These -------------------------------------- further relay the message to one or more effector proteins Effector proteins --------------------mediate the appropriate - response same receptor molecule can interact ------------------------------------------------------------------ intracellular signed so same with only relay systems ------------------------------------------------------=> receptor & same different effects in different cells Same relay system many act on many different intracellular targets By changing the conformation signals --------------------- of a receptor, ----------------- lead to a response inside the cell. produced very 16_08_cascades.jpg Copyright © 2005 Pearson Prentice Hall, Inc.  ↓ important in 16_06_extracellular_sig.jpg apoptosig in the assences of these cells Copyright © 2005 Pearson Prentice Hall, Inc. Fig. 11-6-3 The Three Stages of Signaling EXTRACELLULAR CYTOPLASM FLUID Plasma membrane 1 Reception 2 Transduction 3 Response Recepto r Activation of cellular response Relay molecules in a signal transduction pathway Signaling molecule cligand) Fill in blank question.  Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cellular response: The signal transduction pathway affects 1 Receptor activation: The binding of a 3 the signaling functions and/or amounts of cellular proteins, thereby molecule causes a conformational change in a producing a cellular response. receptor that activates its function. Signaling Intracellula Cellular molecule r respons 2 Signal transduction: The targets e activated receptor stimulates Enzym Altered metabolism Activated a e or receptor series of proteins that forms a other cell functions protein signal transduction pathway. Structura Altered cell shape l or proteins movement Transcription Altered gene factor expression, which changes the Inactive Signal Nucleus types receptor transduction and the amounts of protein pathway proteins in the cell 15 Cell Signalling 16  Reception you will see it o the exam A receptor endogenous ligand Has to have an ----------------------------- high affinity (strength) Has to bind it with ----------------------------- from other similar recognize the biologically ligand active Has to ------------------------------------------- molecules biological response Has to produce the ---------------------- especificity All the conditions have to be met!!!  Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ligand (signaling molecule) Ligan Inactive recepto d bindin r g Activated receptor The binding of a ligand to its receptor causes a conformational change in the receptor, resulting Cytosol in receptor activation. 18 Categories of Receptors Ion channels receptors these will Ligand-gated ion channels ---------------------------- only we talked Voltage gated ion channels About Receptors that are linked to cytoplasmic enzymes Cytokine receptors Receptors that have intrinsic enzymatic activity (they are enzymes) Receptor tyrosine kinases ------------------------------- Receptors that activate intracellular second messengers G-protein coupled receptors ---------------------------- Cell adhesion receptors - ---------------------------------- 16_14_3_basic_classes.jpg Copyright © 2005 Pearson Prentice Hall, Inc.  Cell surface receptors Three kinds: Enzyme-linked receptors (RTK) G-protein coupled receptors (GPCR) Ligand-gated ion channels Enzyme-linked receptors Found in all living species Extracellular domain binds signal Intracellular domain -- becomes functional latalyst protein kinases -Most are 21 Enzyme-linked receptors intracellular domains Many receptors have ---------------------with enzyme function tyrosine- kinases Most are receptor --------------------------- phosphorylate tyrosine They ------------------------------residues in selected intracellular proteins all These receptors are activated by ---------------, growth cell proliferation thus being important in --------------------------- 2 Receptor Tyrosine Kinases Category of enzyme-linked receptors found in animals Recognize various types of signaling molecules hormone thatncts to stimulate Growth factor – -------------------------------------------------- or division all growth ------------------- example: Epidermal Growth Factor (EGF) One function is to stimulate epidermal cells to divide Functions in many different contexts 24 NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health. NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health. RAS multifaceted a recognizeactions various NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.  Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ras - feels cells to KE Y Signaling 1 Receptor activation: Two EGF molecules bind to 2 EGF not die molecules Receptor receptor subunits, causing them Relay to dimerize and phosphorylate proteins 5 Cellular response: Myc and Fos Protein each other on tyrosines. kinases factors stimulate the transcription Transcription of specific genes. The mRNAs Newly made are translated into proteins that proteins cause the cell to progress through the cell cycle and divide. EGF P P P & Translation mRN molecule EGF A s P receptor P P P Loading… Relay P subunit Newly made proteins Fos Gr protein s So s b T involved with cell division My c Ra GD & Erk s P Nucleus Y - P Ra - => P GT P P Erk s Ra P Me Me GD s GT k Ra k P Ra Ra P f f f 2 Relay between the receptor and protein kinase cascade: Protein kinase Grb binds to the phosphorylated cascade 4 Activation of receptor and then to Sos. Sos 3 Protein kinase cascade: transcription factors: stimulates Ras to release GDP Ras activates Raf, which starts a Erk enters the nucleus and bind GTP. turnoncogenes protein kinase cascade in which Raf and phosphorylates can phosphorylates Mek, and then Mek transcription factors, phosphorylates Erk. Myc and Fos. into cer uncontrolled - all growth Signal transduction (steps 2–4) 29  know some of the major Another Example mechanisms inhibitory ↑ protein , inhibits D * apoptosis. 2 molecules ↓ Doesn't interfere with the pro, tein's function NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.  NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health. learn Don't B cell activation  G-protein coupled receptors (GPCR) Found in all eukaryotes, common in animals 7 transmembrane --------------------------segments protein 2 Activated receptor activates --------------- and kinds GiD Releases GDP -----------------------------instead G protein to dissociate GTP causes -------------------------- α subunit and β/γ dimer interact with other proteins Signaline pathway in a ---------------------------- I have separate signaling state 6 protein pathway targets Active ↓ GTP to bond 32  Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2 The G protein exchanges GDP for GTP. The G protein then 1 A signaling molecule binds to dissociates from the receptor and separates into an active a α subunit and a β/ dimer. The activated subunits GPCR, causing it to bind to a promote y G protein. cellular responses. Recepto Signaling r molecule protein S (GPCR) S α β + GTP () GDP GDP Activated Activated Inactive release G protein G protein = G d α β/ protein subunit P dimer i Cytoso 3 The signaling molecule eventually dissociates from the receptor, l and the subunit hydrolyzes GTP into GDP + Pi. The α subunit and the β/ dimer reassociate. Y 33 16_18_Gprot_subunit.jpg Copyright © 2005 Pearson Prentice Hall, Inc.  Signal Transduction and the Cellular Response What produces the cellular response to signals? Typically, the signaling molecule binds to cell surface receptor and the conformation change stimulates a signal transduction pathway Signal transduction pathways may involve a Kinases cascade of intracellular --------------, or generation second messengers of intracellular signals called ------------------------ ↓ helps to increase specificity. 35 G-protein-coupled receptors - Signals binding to cell surface are “first messenger” Many signal transduction pathways lead to production of second messengers They relay signals inside cells Examples: - CAMP - Cast - Diacylglycerol & inositol triphosphate 36  know The Signal transduction via cAMP -persons Of Cyclic adenosine monophosphate prokaryotes indescible Signal binding to GPCR activates G protein to bind GTP,repres , causing dissociation, freeing α subunit Table α subunit binds to adenylyI cyclase enzyme, stimulating ----------------- synthesis of cAMP Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. NH NH NH 2 2 2 N N N N N N H H H H H H N O O O N N O N N N Adenylyl Phosphodiesteras O CH 2 O P O P O P O – cyclase sO CH a e 2 O CH 2 O P HO O O O O O O – – – PP P – O O H2 i (pyrophosphate O & OH OH OH – OH OH z ) G ATP Cyclic AMP (cAMP) AM P second messenger 37  cAMP has two advantages Adeenage speed : ↑⑳ signal amplific Signal amplification ------------------------ cation Binding of signal to one receptor can cause the synthesis of many cAMP molecules that activate PKA, and each PKA can phosphorylate many proteins Speed ------------- In one experiment a substantial amount of cAMP was made within 20 seconds after addition of signal small molecules used are 38  cAMP then activates protein kinase A (PKA) Activated catalytic PKA subunits phosphorylate specific cellular proteins PKA targets include - enzymes - Structural proteins - transcription factors When signaling molecules no longer produced, eventually effects of PKA are reversed 39  cAMP has two advantages Signal amplification Binding of signal to one receptor can cause the synthesis of many cAMP molecules that activate PKA, and each PKA can phosphorylate many proteins Speed In one experiment a substantial amount of cAMP was made within 20 seconds after addition of signal  Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Signal/recepto r cAM P Activate d PKA T T = Target protein phosphorylated by PKA Phosphat e 41 Neuron and cAMP Blue = low levels Yellow = intermediate Purple = high  Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2 The binding of the α subunit to adenylyl cyclase 1 The binding of Activate promotes epinephrine d the synthesis of cAMP from activates a GPCR. adenylyl ATP. This causes the G cyclase protein to bind GTP, 3 cAMP binds to the regulatory subunits thereby promoting of PKA, which releases the catalytic the dissociation of subunits of PKA. the subunit from the β/ dimer. GT > cAMP Epinephrine Epinephrine (signaling (signaling molecule) molecule) P Activate ATP - ↳ P Activate d d G- protein α -IS Zu ATP ADP Phosphorylated protein G- subunit Activate protein d 4 The catalytic subunits of PKA use Activated β/ PKA ATP to phosphorylate specific cellular dimer G-protein-coupled Catalyti Regulatory proteins and thereby cause a cellular receptor (GPCR) c subunits response. subunit Inactive s PKA 43  Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. responsible for Epinephrin e or Skeletal fight Activated Activated muscle flight adenylyl cell GPCR GT cyclase S P Activated G-protein ATP cAM a P subunit S PKA PKA (inactive) (active) - Glycoge - Phosphorylase - Phosphorylas > Glycoge kinase e P n n P (inactive) ATP kinase synthase ATP Synthase (active) (active) (inactive) ATP T Glycogen Glycogen phosphorylas phosphorylas P e e (inactive) (active) ↓ Glycogen Glycogen breakdown synthesis is stimulated. is inhibited. 44  Ligand-gated ion channels Plant and animal cells Ligand binding causes ion channels to open and ions to flow through the membrane - In these animals , transmit synaptic signals between neurons and muscles or between a neurons. 45 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Signaling molecule- -liganda Ions Cytosol The binding of two extracellular signaling molecules (ligands) opens the ion channel, permitting ions to pass through the membrane. 46 Signal transduction via DAG and IP3 Another way for an activated G protein to activate a signal transduction pathway phospholipase α subunit activates --------------- C plasma membrane phos- Phospholipase C cleaves ------------------------------ pholipid (PIDE producing diacylglycerol (DAG) and ---------- inositol triphosphate (IP3) ca' influx causing Ca2+ channels in ER open, --------------------- Ca2+ exerts a variety of effects on cell behavior 47  Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Membrane phospholipid DA (PIP2) G with inositol head group 2 The α subunit of this G protein binds to phospholipase C, causing it to cleave Activated a bond in a membrane phospholipid, PKC IP3 and producing DAG and IP3. released ATP GT AD into cytosolIP Protein 4 Binding of DAG and Ca2+ P Activated 3 P a to PKC activates PKC, that phospholipase causes which C a cellular then phosphorylates Signaling Activated proteins and leads to a response Ca2 G-protein Ca2+ molecule + cellular response. α channe l Activated Activated G- subunit calmodulin protein- coupled receptor 3 Binding of IP3 to Ca2+ (GPCR) channels in the ER causes 1 A signaling molecule 4 Binding of Ca2+ to them to open and release activates a GPCR, many Ca2+ into the b calmodulin thereby cytosol. activates its function, which activating the α subunit regulates proteins and also of the G protein (see leads to a cellular response. Figure 9.7). Endoplasmi c reticulum 48  NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health. B cell activation Intracellular Receptors found in Some receptor proteins are intracellular, -------------. cy tosol or nucleus of alls ------------------------------------ target 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 hormon-receptor complex can act ----------------------------------------------------------- as a transcription factor Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings  Intracellular receptors Some receptors are inside the cell Example: Estrogen Hormone passes through cell membrane and into the nucleus where it binds estrogen receptor The estrogen receptor complex binds DNA and regulates gene transcription Intracellular receptors 2 Estrogen receptors form a dimer, bind next to specific genes, and activate their transcription. The mRNAs are then translated into proteins that affect the structure and function of the cell. Estroge n Protein that Active Active affects cell estrogen estrogen structure and receptor receptor dimer dimer function mRN A Inactive estroge n receptor Chromosoma Chromosoma ll DNA DNA Nucleus 1 Estrogen diffuses across the plasma membrane, enters the nucleus, and binds to the estrogen receptors. The receptors undergo a conformational change. 52 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Hormonal Signaling in Multicellular Organisms The response to a given signaling molecule depends on which cell is responding - The response determined the set by variation in is of that each all makes (the proteins proteome 53 example: Epinephrine Fight-or-flight hormone Different effects throughout body Airways of the & lungs relax to provide more oxygen Heart muscle cells beat faster & More glycogen breakdown in skeletal muscle & have - receptors for epinephrine This explains effect of caffeine Caffeine inhibits phosphodiesterase, the enzyme that removes cAMP once the signal is gone Inhibition causes cAMP to persist, so heart beats faster even with low epinephrine 54  Table 9.1 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education. Table 9.1 Effect of Epinephrine in Humans Organ/Tissue Effect Eye Dilates pupils Salivary glands Inhibits the production of saliva Skeletal muscle Stimulates cells to break down glycogen and release glucose Skin Constricts blood vessels; stimulates sweating Lungs Relaxes airways so more oxygen is taken in Heart Increases the rate of beating  A Cell’s Response to Hormones and Other Signaling Molecules Depends on the Proteins It Makes One hormone causes different effects in different cell types expression Differential gene r -------------------------– all cells contain the same genome but only express particular genes Can effect cellular response in a variety of ways - Receptor may not be expressed Different receptors for same - signal - Different affinities for Signal - signal transduction pathways different