Cell Communication PDF Lecture Notes

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University of Nicosia Medical School

Chris Romero

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cell communication biology lectures signaling pathways cell biology

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These lecture notes cover cell communication, including local (cell junctions, cell-cell recognition, local regulators) and long-distance (hormones) signaling. The notes detail the three stages of cell signaling (reception, transduction, and response), with examples of intracellular and plasma membrane receptors and second messengers. Diagrams and figures illustrate the concepts.

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Topic 7 Cell Communication PowerPoint Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Lectures by Chris Romero Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Learning objectives 1. Explain the mechanisms by which cells communicate with each o...

Topic 7 Cell Communication PowerPoint Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Lectures by Chris Romero Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Learning objectives 1. Explain the mechanisms by which cells communicate with each other in local vs distal signalling. 2. Describe the stages of the cell signalling process. 3. Identify the different types of intracellular and plasma membrane receptors and describe their function. 4. Describe the role of second messengers in the cell signalling cascades. Topic 5 (week 5 LOB): Identify the different types of intercellular junctions in animal cells vs plant cells and their function. Required reading: Chapter 9 (Campbell) Additional reading: Alberts et al, Molecular Biology of the Cell (Ch19). Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell communication: overview Intercellular (cell-to-cell) communication is essential for multicellular organisms Biologists have discovered some universal mechanisms of cellular regulation Similar mechanisms in microbes and mammals, suggesting an early origin For example, the dilation of blood vessels is controlled by multiple molecules Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Signal transduction pathways Signal transduction pathways: convert extracellular signals into cellular responses 2 types of cell communication: Local signalling: neighbouring cells communicate though cell junctions, cell-to-cell recognition or local regulators Long distance signalling: distant cells in multicellular organisms communicate using chemical messengers (e.g. hormones) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings I. Local signaling In local signaling, cells may communicate by: – Direct contact: via cell junctions (animal and plant cells) – Cell-cell recognition: via surface molecules (animal cells only) – Local regulators: in paracrine/synaptic signaling (animal cells only) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 1. Local signaling: Direct contact with cell junctions Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells Cell junctions coordinate the function of neighbouring cells in a tissue Plasma membranes Gap junctions Plasmodesmata between animal cells between plant cells Figure 9.3 (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 2. Local signaling: cell-cell recognition In local signaling, animal cells communicate and recognize each other via direct contact using surface molecules (e.g. membrane carbohydrates) Figure 9.3 (b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 3. Local signaling: communication by local regulators Paracrine and synaptic signaling: animal cells communicate using local regulators Local regulators: messenger molecules that travel only short distances (e.g. growth factors, neurotransmitters) Local signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter Secretory diffuses across vesicle synapse Local regulator diffuses through Target cell extracellular fluid is stimulated (a) Paracrine signaling. A secreting cell acts (b) Synaptic signaling. A nerve cell on nearby target cells by discharging releases neurotransmitter molecules molecules of a local regulator (a growth into a synapse, stimulating the factor, for example) into the extracellular target cell. Figure 9.4 fluid. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cell junction types: cell-to-cell connection Communicating junctions: - Gap junctions: in animal cells, no cytoskeletal connection - Plasmodesmata: in plant cells, no cytoskeletal connection Occluding junctions: -Tight junctions: connect with actin microfilaments Anchoring junctions: - Desmosomes: connect with intermediate filaments - Adherens junctions: connect with actin microfilaments Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Plant cell junctions: plasmodesmata Channels connecting neighbouring cells Allow cell communication and molecule exchange (e.g. small molecules and water) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Types of intercellular junctions in animals Tight junctions: prevent intercellular communication (material exchange) Desmosomes: anchor cells through ECM Gap junctions: - channels between cells - allow molecule exchange between cells Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 1. Gap junctions: communicating junctions Cytoplasmic channels made by membrane proteins (connexins) connecting adjacent cells Necessary for cell-to-cell communication Allow small molecule and ion exchange between cells (e.g. cAMP, Ca+2) Located along the apical surfaces of cells of various tissues (e.g. epithelial cells and heart muscle) Transport of Ca+2 between neighbouring smooth muscle cells through gap junctions  Synchronized contraction of intestine and uterus during birth Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 1. Gap junctions: structure Gap connexin junction channel cytoplasm cytoplasm Connexin Intercellular subunit gap Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 2. Tight junctions: occluding junctions Underneath the apical surface of epithelial cells Inhibit cell-to-cell communication (molecule exchange) Create an exclusion zone around the cells => prevent leakage of extracellular fluid from a layer of epithelial cells (e.g skin layer) Made by 2 types of transmembrane proteins: - Claudin and occludin Τhe cytoplasmic part of occludin is linked to the actin microfilaments Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 2. Tight junctions: structure microvilli Protein junction of adjacent cells Tight junction Series of Inter- occludin and cellular claudin space Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 3. Anchoring junction types Connect neighbouring cells (Cell-to-cell connection): - Desmosomes - Adherens junctions Connect cells with ECM (Cell to ECM connection): - Focal adhesions - Hemidesmosomes Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 3. Anchoring junctions structure Transmembrane adhesion (linker) proteins= cadherins/ integrins Cytoskeletal filaments: - actin filaments (in adherens junctions/ focal adhesions) - intermediate filaments (in desmosomes/ hemidesmosomes) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 3. Anchoring junctions: desmosomes and adherens junction structure Cytoskeletal filaments Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 3. Desmosomes: anchoring junctions Function like rivets fastening cells together into strong sheets Anchor to the cytoplasm though intermediate filaments (e.g. keratin) Connect cells via transmembrane adhesion proteins (cadherins) Desmosomes connect with: - Keratin intermediate filaments in epithelial cells - Desmin intermediate filaments in heart muscle cells and smooth muscle cells Desmosomes attach muscle cells to each other in a muscle => Some ‘muscle tears’ involve the rupture of desmosomes Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 3. Desmosomes in epithelial cells: structure Attachment protein = desmoplakin Adhesion protein = cadherin Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 3. Adherens junctions Create an adhesion zone (belt) underneath the apical surface of epithelial cells Connect the plasma membranes of neighbouring cells via transmembrane adhesion proteins (cadherins) Intracellular attachment proteins (catenins, vinculin, α- actinin): connect cadherins with actin microfilaments Cell 1 Plasma Cell 2 membranes actin Cadherin Attachment microfilaments dimers proteins Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 3. Adherens junctions Adherens junctions in intestinal epithelial cells Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 3. Adherens junctions vs desmosomes ADHERENS JUNCTION DESMOSOME Actin Intermediate microfilaments filaments Attachment proteins Cytoplasm Intercellular space Cadherins Cytoplasm Attachment Intermediate Actin proteins filaments microfilaments Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 3. Anchoring junctions: Cell –ECM connection Focal adhesions (contacts): - Extracellular connection: Connect cells to the ECM through integrins (transmembrane proteins) - Intracellular connection: Integrin cytoplasmic domain connects with actin microfilaments through attachment proteins (talin, α- actinin, vincoulin) Hemidesmosomes: - Found mainly in basal surface of epithelial cells - Extracellular connection: Stabilise epithelial cells by anchoring them to the ECM through integrins (transmembrane proteins; integrin binds to basement membrane laminin) - Intracellular connection: connect with keratin intermediate filaments through attachment proteins (plectin) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 3. Focal adhesions and hemidesmosomes Keratin Epithelial Integrin filaments cell Plasma Attachment (cytoplasm) membrane proteins Basement membrane (ECM type, Laminin extracellular space) Plasma membrane Collagen Attachment proteins Focal adhesion Hemidesmosome Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 3. Desmosomes and hemidesmosomes basement membrane Basement membrane (basal lamina): specialized ECM type that separates an endothelial cell layer form the underlying connective tissue Desmosomes and Connective tissue: consists mostly of ECM secreted by hemidesmosomes in the fibroblasts intestinal epithelial cells Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 3. Desmosomes and hemidesmosomes: structure Desmosome vs hemidesmosome structure - Transmembrane protein: cadherin in desmosomes, integrin in hemidesmosomes - Extracellular attachment: cadherins of the other cell in desmosomes, ECM in hemidesmosomes Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 3. Anchoring junctions: summary Cell-cell (cell-cell) Focal adhesions Cell-ECM (plectin) (cell-matrix) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Alberts et al, Molecular Biology of the Cell Summary of animal cell junctions: cytoskeleton connection Apical surface Cell-cell Basal surface Cell-ECM (ECM type) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Summary of animal cell junctions: function (claudins and occludins) Adherens junctions Anchors actin microfilaments to the Focal adhesions basal lamina (ECM type) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings II. Long-distance signaling In long-distance signaling, both plants and animals use hormones Hormonal signaling in animals: Long-distance signaling Endocrine cell Blood - also known as endocrine signaling vessel - specialized cells release hormone molecules which travel via the circulatory system to target cells in Hormone travels in bloodstream other parts of the body to target cells Target cell (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all Figure 9.4 C body cells. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Three Stages of Cell Signaling Three stages of cell signaling: 1. Reception 2. Transduction 3. Response Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Overview of cell signaling EXTRACELLULAR CYTOPLASM FLUID Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signaling molecule Figure 9.5 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 1. Reception Reception: the signaling molecule binds to a receptor protein, causing it to change shape (conformational change) The receptor protein conformational change initiates the process of transduction EXTRACELLULAR CYTOPLASM FLUID Plasma membrane 1 Reception Receptor Signaling molecule Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 1. Reception The binding between the signal molecule (ligand) and receptor is highly specific Receptor types: - Plasma membrane receptors - Intracellular receptors Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Intracellular Receptors Intracellular receptors: cytoplasmic or nuclear proteins Signaling molecules that are small or hydrophobic and can readily cross the plasma membrane use these receptors Example: steroid hormones bind to intracellular receptors Steroid hormones: estrogens (e.g. estradiol) and androgens (e.g. testosterone) Steroid hormone receptors: e.g. Estrogen receptors (ERs) and androgen receptors (ARs) Clinical correlation: tamoxifen - Drug used for treatment of ER+ breast cancer - Mode of action: Estrogen antagonist (binds to the ER and prevents estradiol binding) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Steroid hormones act via intracellular receptors Steroid hormone EXTRACELLULAR (e.g.estradiol) FLUID 1 The steroid hormone (e.g. testosterone or estradiol) passes through the plasma membrane. Plasma membrane 2 The hormone binds Receptor to a receptor protein protein in the cytoplasm, Hormone- activating it. receptor complex 3 The hormone- receptor complex enters the nucleus and binds to specific DNA genes. mRNA 4 The bound protein stimulates the transcription of the gene into mRNA. NUCLEUS New protein 5 The mRNA is translated into a specific protein. Figure 9.6 CYTOPLASM Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Plasma Membrane Receptors There are three main types of plasma membrane receptors: – G-protein-coupled – Tyrosine kinases – Ion channels Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G protein-coupled receptors G protein-coupled receptors: plasma membrane receptors linked to a G protein G-proteins: proteins bound to GTP/GDP G proteins act as an on/off switch: – If GDP is bound to the G protein => G protein is inactive – If GTP is bound to the G protein => G protein is active Involved in many human diseases, including bacterial infections Example: cholera toxin and botulinum toxin are bacterial products that interfere with G protein function More than 60% of all medicines used today exert their effects by influencing G protein pathways Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G-protein-coupled receptors Signal-binding site Segment that G-protein coupled receptors: interacts with G proteins transmembrane proteins G-protein-linked Activated Inactivated Plasma Membrane Signal molecule Receptor Receptor enzyme GDP G-protein GDP GTP CYTOPLASM (inactive) Enzyme Activated enzyme GTP GDP Pi Cellular response Figure 9.7 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Receptor tyrosine kinases Protein kinases: enzymes that phosphorylates protein substrates (adds phosphate groups to them) Receptor tyrosine kinases: transmembrane receptors that attach phosphates to tyrosine residues 2 domains: - Extracellular ligand binding domain - Intracellular domain with tyrosine kinase activity Growth factor receptors are commonly receptor tyrosine kinases (e.g. EGFR, PDGFR, etc) Growth factor binding to their receptor tyrosine kinases => Activation of signal transduction pathways such as the MAPK pathway (MAPK=Mitogen Activated Protein Kinase) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Receptor tyrosine kinases Figure 9.7 Ligand binding => receptor dimerization Signal Signal-binding site molecule Signal -helix in the molecule Membrane Tyr Tyr Tyr Tyr Tyr Tyr Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine CYTOPLASM kinase proteins Dimer (inactive monomers) Activated relay proteins Cellular Tyr Tyr P Tyr Tyr P P Tyr Tyr P Tyr P response 1 Tyr Tyr P Tyr Tyr P P Tyr Tyr Tyr P Tyr Tyr P P Tyr Tyr P Cellular 6 ATP 6 ADP response 2 Activated tyrosine- Fully activated receptor kinase regions tyrosine-kinase Inactive (unphosphorylated (phosphorylated relay proteins dimer) dimer) Autophosphorylation of tyrosine Phosphorylation of other proteins residues => activation => Activation of signal transduction Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings pathways (e.g. MAPK pathway) Receptor tyrosine kinases: clinical correlations Abnormal tyrosine kinase receptors may contribute to some kinds of cancer - truncated receptors that function in the absence of signaling molecules (lack the ligand-binding domain) - overexpression/ amplification of receptors: - Example: EGFR (Epidermal Growth Factor Receptor) amplification (overexpression) in many cancers (e.g. breast cancer) Several anti-cancer drugs block tyrosine kinase activity (herceptin, Gleevec) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ion channel receptors Ligand-gated ion channel Signal Gate Ions closed molecule receptors: acts as a gate (ligand) which opens when the receptor changes shape Ligand-gated Plasma ion channel receptor Membrane 1. Binding of signaling Gate open molecule (ligand) to the receptor 2. Receptor changes shape Cellular (the gate opens) response 3. Specific ions (e.g. Na+, Gate close Ca2+) pass through a channel in the receptor Figure 9.7 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 2. Transduction Transduction: the signal from the receptor converted to a form that can cause a specific cellular response Transduction usually requires a series of changes in a series of different target molecules EXTRACELLULAR CYTOPLASM FLUID Plasma membrane 1 Reception 2 Transduction Receptor Relay molecules in a signal transduction pathway Signaling molecule Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 2. Transduction Signal transduction pathways: - cascades of molecular interactions that relay signals from receptors to target molecules in the cell - At each step in a pathway the signal is transduced into a different form (usually a conformational change in a protein) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Protein Phosphorylation and Dephosphorylation Many signal pathways include phosphorylation cascades (e.g. MAPK signaling pathway) In this process: – Protein kinases: enzymes that add a phosphate to the next protein kinase in line => activate protein kinases – Phosphatases: enzymes that remove the phosphates => deactivate the protein kinases Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings A phosphorylation cascade Signal molecule Receptor Activated relay 1 A relay molecule molecule activates protein kinase 1. Inactive protein kinase 2 Active protein kinase 1 1 Active transfers a phosphate from ATP protein to an inactive molecule of kinase protein kinase 2, thus activating 1 this second kinase. Inactive protein kinase ATP 2 ADP Active P 3 Active protein kinase 2 protein then catalyzes the phos- PP kinase phorylation (and activation) of Pi 2 protein kinase 3. Inactive protein kinase ATP 3 ADP Active P 4 Finally, active protein protein kinase 3 phosphorylates a 5 Enzymes called protein kinase protein (pink) that brings phosphatases (PP) PP Pi 3 about the cell’s response to catalyze the removal of the phosphate groups Inactive the signal. from the proteins, protein ATP ADP P making them inactive Active Cellular and available for reuse. protein response PP Pi Figure 9.8 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Second Messengers: Small Molecules and Ions Second messengers: small, non-protein, water-soluble molecules or ions that acts in the signal transduction pathways Examples: - cAMP - Ca+2 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cyclic AMP Cyclic AMP (cAMP): – Produced from ATP through the enzyme adenylyl cyclase NH2 NH2 NH2 N N N N N N O O N N N N O N N O Adenylyl cyclase Phoshodiesterase – HO P O CH2 O P O P O P O Ch2 CH2 O− O− O− O O O O O− O Pyrophosphate P H2O P Pi O− O OH OH OH OH OH ATP Cyclic AMP AMP Figure 9.9 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cyclic AMP Many G-proteins trigger the formation of cAMP cAMP then acts as a second messenger in the signal transduction pathways First messenger (signal molecule such as epinephrine) Adenylyl G protein cyclase G-protein-linked GTP receptor ATP cAMP Protein kinase A Cellular responses Figure 9.10 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Calcium ions Calcium ions (Ca+2), when released into the cytosol of a cell, acts as a second messenger in many different pathways Calcium is an important second messenger because cells are able to regulate its concentration in the cytosol EXTRACELLULAR Plasma FLUID membrane Ca2+ ATP pump Mitochondrion Nucleus CYTOSOL Ca2+ pump Endoplasmic ATP Ca2+ reticulum (ER) pump Figure 9.11 Key High [Ca2+] Low [Ca2+] Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Inositol Triphosphate (IP3) and Diacylglycerol (DAG) Other second messengers: - Diacylglycerol (DAG) - Inositol triphosphate (IP3) IP3 triggers an increase in calcium concentration in the cytosol Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Second messengers: Ca+2, IP3 and DAG 1 A signal molecule binds 2 Phospholipase C cleaves a 3 DAG functions as to a receptor, leading to plasma membrane phospholipid a second messenger activation of phospholipase C. called PIP2 into DAG and IP3. in other pathways. EXTRA- Signal molecule CELLULAR (first messenger) FLUID G protein DAG Activates PKC GTP Calcium release G-protein-linked PIP2 from the ER to receptor Phospholipase C IP3 (second messenger) the cytosol through gated ion IP3-gated channels calcium channel Endoplasmic Various Cellular reticulum (ER) Ca2+ proteins response activated Ca2+ (second messenger) 4 IP3 quickly diffuses through 5 Calcium ions flow out of 6 The calcium ions the cytosol and binds to an IP3– the ER (down their con- activate the next gated calcium channel in the ER centration gradient), raising protein in one or more Figure 9.12 membrane, causing it to open. the Ca2+ level in the cytosol. signaling pathways. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Phosphoinositides: Inositol phospholipids Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Alberts et al, Molecular Biology of the Cell Phosphoinositides breakdown by PLC Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Alberts et al, Molecular Biology of the Cell 3. Response Response: the transduced signal triggers a specific cellular response Cell signaling leads to regulation of cytoplasmic activities (cytoplasmic response) or transcription (nuclear response) EXTRACELLULAR CYTOPLASM FLUID Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signaling molecule Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cytoplasmic response to a signal In the cytoplasm, signaling pathways regulate a variety of cellular activities Reception Example: Glycogen Binding of epinephrine to G-protein-linked receptor (1 molecule) breakdown into glucose 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 Figure 9.13 (108 molecules) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Nuclear response to a signal Other pathways regulate genes by activating transcription factors that turn gene expression on or off Example: steroid hormone signaling pathways, MAPK signaling cascade Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription Active factor transcription Response factor P DNA Gene NUCLEUS mRNA Figure 9.14 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Regulation of the Response Multistep signaling pathways have two important benefits: – Amplification of the signal => amplification of the response – Contribution to the specificity of the response  Provide more opportunities for coordination and regulation Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Signal Amplification Each protein in a signaling pathway amplifies the signal by activating multiple copies of the next component in the pathway At each step, the number of activated products is much greater than in the preceding step Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Specificity of Cell Signaling Different kinds of cells have different types of proteins Different proteins allow cells to detect and respond to different signals => Even the same signal can have different effects in cells with different proteins and pathways The different combinations of proteins in a cell give the cell great specificity in both the signals it detects and the responses it carries out Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Pathway branching and “cross-talk” Pathway branching and “cross-talk” further help the cell to coordinate incoming signals Signal molecule Receptor Relay molecules Response 1 Response Response Cell A. Pathway leads Cell B. Pathway branches, 2 3 to a single response leading to two responses Activation or inhibition Response 4 Response 5 Cell C. Cross-talk occurs Cell D. Different receptor Figure 9.15 between two pathways leads to a different response Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Signaling Efficiency: Scaffolding Proteins and Signaling Complexes Scaffolding proteins: - Large relay proteins to which other relay proteins are attached - Function: increase the signal transduction efficiency by grouping together different proteins involved in the same pathway Signal molecule Plasma  more efficient membrane activation of Receptor Three signaling pathways different protein Scaffolding kinases protein Figure 9.16 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Termination of the Signal Signal response is terminated quickly – By the reversal of ligand binding => Ligand released from the receptor Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Visual aids Signaling molecules: http://www.youtube.com/watch?v=tMMrTRnFdI4&feature=related https://www.youtube.com/watch?v=FtVb7r8aHco The MAPK signalling pathway http://www.youtube.com/watch?v=r7GoZ9vFCY8&feature=related Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Summary Cells communication: - Local signalling: cell junctions, cell-cell recognition, local regulators - Distal signalling: hormones 3 stages of cell signalling: reception, transduction, response 1. Reception: Intracellular receptors: cytoplasmic or nuclear Plasma membrane receptors: G-protein coupled, receptor tyrosine kinases, ion channels 2. Signal transduction: second messengers (cAMP, Ca+2, DAG, IP3) 3. Response: cytoplasmic or nuclear Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

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