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Transcript
10/7/2015 Chapter 11: Cell Communication 1. Overview of Cell Communication 2. Receptors: Receiving the Signal 3. Signal Transduction 4. Responding to the Signal 1. Overview of Cell Communication Chapter Reading – pp. 211-214 Cell Communication in Microbes factor Receptor 1 Exchange of mating factors a • intercellular signaling occurs in single-celled microbes and has likely been around a long time a factor 1 Individual Yeast cell, rod-shaped matingcells type Yeast cell, mating type a 2 Mating a Aggregation in progress 0.5 mm 3 Spore-forming structure (fruiting body) 3 New a/ cell 2.5 mm a/ Fruiting bodies 1 10/7/2015 Soluble Signals in Multicellular Organisms 3 basic types: 1) endocrine • signal acts from a distance • hormones are “endocrine” 2) paracrine • signal acts locally, on nearby cells 3) autocrine • signal acts on source cell (“self-stimulation”) Endocrine Signaling Long-distance signaling Endocrine cell Soluble molecular signals a released that travel throughout a multicellular organism via circulatory system • hormones released by glands in the endocrine system Blood vessel Hormone travels in bloodstream to target cells Target cell (c) Hormonal signaling Local Signaling • release of soluble signal molecules that act locally Paracrine signaling Synaptic signaling Target cell Secreting cell Local regulator diffuses through extracellular fluid Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Secretory vesicle Target cell is stimulated 2 10/7/2015 Autocrine Signaling Autocrine signals activate receptors on the cell producing the signal Signaling through Cell-Cell Contact Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells • signals can be passed between cells via junctions linking the cytosol (a) Cell junctions • membrane-bound ligands can bind to receptors on adjacent cells (b) Cell-cell recognition Stages of Cell Signaling Signaling between cells occurs in 4 general steps: 1) Signal molecule “released” from source cell 2) Signal molecule received by target cell 3) Signal relayed to cell interior 4) Signal reaches target, cell responds* *Cell responses include changes in gene expression or changes in the activity of proteins or other macromolecules 3 10/7/2015 Responding to the Signal The trick is getting the signal received transmitted to the target within the cell: CYTOPLASM EXTRACELLULAR FLUID Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signaling molecule 2. Receptors: Receiving the Signal Chapter Reading – pp. 214-218 Common Types of Receptors Listed below are common types of membrane receptor proteins that transmit signal to the interior of a cell when bound to ligand: G protein-coupled receptors (GPCRs) • associated with intracellular G proteins Receptor Tyrosine Kinases (RTKs) • phosphorylate intracellular tyrosine residues Ion Channel Receptors • receptors that also function as ion channels Steroid Hormone Receptors • intracellular receptors that bind hormones 4 10/7/2015 Kinases & Transcription Factors Key targets of most signaling pathways are various kinases & transcription factors (TFs). Kinases: • enzymes that “phosphorylate” (add a phosphate to) very specific substrates • phosphorylate either serine or threonine residues (serine/threonine kinases) or tyrosines (tyrosine kinases) • can activate or inhibit substrate Transcription Factors: • proteins that regulate transcription of specific genes there are also important phosphatases (remove phosphates) G Protein-Coupled Receptors These are integral membrane proteins that bind a specific ligand on the exterior of the cell and interact with G proteins on the cytoplasmic side of the membrane. Signaling-molecule binding site Segment that interacts with G proteins G proteins are activated to transmit signal when GPCR binds ligand G protein-coupled receptor G Proteins • inactive when bound to GDP, active when bound to GTP Plasma membrane G protein-coupled receptor Activated receptor Signaling molecule Inactive enzyme GDP CYTOPLASM GDP Enzyme G protein (inactive) GTP 2 1 Activated enzyme GTP GDP Pi Cellular response 3 4 5 10/7/2015 Receptor Tyrosine Kinases Ligand-binding site Signaling molecule (ligand) Helix Signaling molecule Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins CYTOPLASM Tyr Tyr Tyr Tyr Dimer 1 2 Activated relay proteins Tyr Tyr Tyr Tyr Tyr Tyr 6 ATP 6 ADP Activated tyrosine kinase regions P Tyr P Tyr P Tyr Gate closed Ions Plasma membrane Gate open Cellular response 3 Tyr P Tyr P Tyr P Tyr P P P Tyr P Tyr Tyr P P Cellular response 1 Cellular response 2 Inactive relay proteins 4 Ligand-gated ion channel receptor 2 Tyr Fully activated receptor tyrosine kinase 3 1 Signaling molecule (ligand) Tyr Gate closed Ion Channel Receptors Many ion channels are gated, i.e., they contain a “gate” which can block the channel. By default, the gate may be closed (or open) only to open (or close) when a soluble signaling molecule is bound to the channel. Steroid Hormone Receptors Steroid hormones are released into the blood from distant sites. They are lipid soluble (hydrophobic), and pass directly through membranes. The receptors they bind are intracellular receptors which become active upon binding. Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA mRNA NUCLEUS New protein CYTOPLASM 6 10/7/2015 3. Signal Transduction Chapter Reading – pp. 218-222 What is Signal Transduction? The process by which a signal received at the cell surface is transmitted to the intracellular target of that signal. Common signal transduction pathways involve: Phosphorylation Cascades • sequential phosphorylation of molecules Second messengers: • cyclic AMP (cAMP) • inositol triphosphate (IP3) • calcium Cascades of Phosphorylation Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP Pi P Active protein kinase 2 PP Inactive protein kinase 3 ATP ADP Pi Active protein kinase 3 PP Inactive protein P ATP P ADP Pi PP Active protein Cellular response 7 10/7/2015 Cyclic AMP Cyclic AMP is adenosine monophosphate in which the phosphate group is covalently bound to two carbons in the sugar ribose. • produced upon activation of the enzyme Adenylyl Cyclase Adenylyl cyclase Phosphodiesterase Pyrophosphate P Pi ATP AMP cAMP Cyclic AMP & Protein Kinase A First messenger Adenylyl cyclase G protein G protein-coupled receptor • some G proteins activate adenylyl cyclase and cAMP production GTP ATP cAMP Second messenger Protein kinase A • cAMP in turn activates Protein Kinase A which phosphorylates key targets Cellular responses Calcium as a 2nd Messenger EXTRACELLULAR FLUID Plasma membrane Ca2+ pump ATP Mitochondrion Calcium ions are generally maintained at a lower concentration in the cytosol relative to the extracellular environment and the endoplasmic reticulum • release of calcium stores from ER or outside the cell is part of some signaling pathways Nucleus CYTOSOL Ca2+ pump Endoplasmic reticulum (ER) ATP Ca2+ pump Key High [Ca2+] Low [Ca2+] 8 10/7/2015 Inositol Triphosphate & Calcium EXTRACELLULAR FLUID Signaling molecule (first messenger) G protein DAG GTP G protein-coupled receptor Phospholipase C PIP2 IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) Various proteins activated Ca2+ Cellular responses Ca2+ (second messenger) CYTOSOL 4. Responding to the Signal Chapter Reading – pp. 223-230 Growth factor Reception Receptor Phosphorylation cascade Changes in Gene Expression Transduction CYTOPLASM Inactive transcription factor Active transcription factor P Response DNA Signal transduction frequently changes gene expression by activating (or inhibiting) transcription factors Gene NUCLEUS mRNA 9 10/7/2015 Amplification of Signals Reception Binding of epinephrine to G protein-coupled receptor (1 molecule) Transduction Inactive G protein This example shows how binding to a single molecule of ligand results in a 108-fold amplification of the original signal • this example also shows how signal transduction results in the activation of a type of enzyme in the cytoplasm Signaling molecule 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) Variety in Signaling Response Receptor Relay molecules Response 1 Cell A. Pathway leads to a single response. Response 2 Response 3 Cell B. Pathway branches, leading to two responses. Different cell types can respond in different ways to the same external signal. • the same receptor-ligand complex can be linked to different intracellular signal transduction pathways in different cells Activation or inhibition Response 4 Cell C. Cross-talk occurs between two pathways. Response 5 Cell D. Different receptor leads to a different response. Apoptosis & Cell Signaling… Apoptosis is also known as “Programmed Cell Death”. Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Apoptosis can be activated in a variety of ways including the binding of an extracellular signal. Receptor for deathsignaling molecule Ced-4 Ced-3 Inactive proteins (a) No death signal 10 10/7/2015 …Apoptosis & Cell Signaling Ced-9 (inactive) Cell forms blebs Deathsignaling molecule Active Ced-4 Active Ced-3 Activation cascade Other proteases Nucleases (b) Death signal Apoptosis is part of Normal Development 1 mm Interdigital tissue During embryonic development, many cells must die by apoptosis in order for a structure or organ to form properly. • loss of webbing between toes and fingers • loss of neurons during brain and nerve development Key Terms for Chapter 11 • endocrine, paracrine, autocrine signals, ligand • G protein receptors, kinase, phosphatase • receptor tyrosine kinases, ion channel receptors • signal transduction, signal cascade • 2nd messengers, cyclic AMP, protein kinase A • inositol triphosphate (IP3), phospholipase C • signal amplification • apoptosis Relevant Chapter Questions 1-5, 7, 8, 10 11