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Cell Communication PowerPoint® Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Cell-to-cell communication is essential for multicellular organisms Universal mechanisms of cellular regulation Combined effects of multiple signals determine cell response Example: dilation of blood vessels is controlled by many molecules • Nitric oxide • Myosin • Signaling molecule called MAP kinase Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response Microbes are a window on the role of cell signaling in the evolution of life Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-2 factor Receptor 1 Exchange of mating factors a a factor Yeast cell, mating type a 2 Mating 3 New a/ cell Yeast cell, mating type a a/ Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes Concentration of signaling molecules allows bacteria to detect population density • Cluster together • Coordination of activities Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-3 1 Individual rodshaped cells 2 Aggregation in process 0.5 mm 3 Spore-forming structure (fruiting body) Fruiting bodies In multicellular organisms, long distance communication is by chemical messengers Local signaling • intercellular connections (plasmodesmata and gap junctions) connect the cytoplasm of adjacent cells • communicate by direct contact, or cell-cell recognition Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Local Fig. 11-4 Plasma membranes Gap junctions between animal cells (a) Cell junctions (b) Cell-cell recognition Plasmodesmata between plant cells In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances In long-distance signaling, plants and animals use chemicals called hormones Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-5 Local signaling Long-distance signaling Electrical signal along nerve cell triggers release of neurotransmitter Target cell Secreting cell Local regulator diffuses through extracellular fluid (a) Paracrine signaling Endocrine cell Neurotransmitter diffuses across synapse Secretory vesicle Target cell is stimulated Blood vessel Hormone travels in bloodstream to target cells Target cell (b) Synaptic signaling (c) Hormonal signaling Earl W. Sutherland discovered how the hormone epinephrine acts on cells • 1971 Nobel Prize Cells receiving signals went through three processes: • Reception (detection of signaling molecule) • Transduction (converts signal to relay or form that can bring about cell change) • Response (enz. catalysis, cytoskeleton mvmt. gene activation) Animation: Overview of Cell Signaling Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-6-1 EXTRACELLULAR FLUID 1 Reception Receptor Signaling molecule CYTOPLASM Plasma membrane Fig. 11-6-2 CYTOPLASM EXTRACELLULAR FLUID Plasma membrane 1 Reception 2 Transduction Receptor Relay molecules in a signal transduction pathway Signaling molecule Fig. 11-6-3 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 Binding between signal molecules (ligands) and receptors = highly specific Shape change in receptor -- initial transduction of the signal Most signal receptors are plasma membrane proteins • Receptors for testosterone or estrogen are cytoplasmic Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Water-soluble signal molecules bind to specific receptors in plasma membrane • insulin 3 main types of membrane receptors: • G protein-coupled receptors • Receptor tyrosine kinases • Ion channel receptors Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Widespread & diverse functions • Highly conserved throughout evolution • vision & smell Plasma membrane receptor that requires a G protein • acts as an on/off switch: when GDP is bound, the G protein is inactive • When GTP is bound, G protein is active Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-7a Signaling-molecule binding site Segment that interacts with G proteins G protein-coupled receptor Fig. 11-7b 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 Hormones & neurotransmitters Bacterial toxins (cholera, pertussis, botulism) interfere w/ G proteins Plasma membrane receptors that attach phosphates to tyrosines Cell growth & cell reproduction • Example: vascular endothelial growth factor (VEGF) stimulates endothelial cells to undergo cell division and migration to form new blood vessels Ligand binding triggers multiple signal transduction pathways at once • Key difference from G protein coupled receptors Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-7c Ligand-binding site Signaling molecule (ligand) Signaling molecule Helix Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins CYTOPLASM Dimer 1 2 Activated relay proteins Tyr Tyr Tyr Tyr P Tyr P Tyr Tyr Tyr P 6 ATP Activated tyrosine kinase regions 6 ADP Tyr Tyr P Tyr Tyr P Tyr P Tyr P Tyr Tyr P P P P Tyr P Tyr Fully activated receptor tyrosine kinase Inactive relay proteins 3 4 Cellular response 1 Cellular response 2 Acts as a gate when the receptor changes shape upon binding ligand - allows specific ions (Na+, K+, Cl- or Ca2+) through the channel in the receptor Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-7d Na+/K+ ATPase Ligand gated ion channels -neurotransmitters in CNS -acetylcholine at the neuromuscular junction 1 Signaling molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor 2 Plasma membrane Gate open Cellular response 3 Gate closed Found in the cytosol or nucleus of target cells Small or hydrophobic chemical messengers can readily cross the membrane to activate receptors • Examples: steroid and thyroid hormones Activated hormone-receptor complex can act as a transcription factor, turning on specific genes Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-8-3 Hormone (testosterone) Intracellular receptors EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA NUCLEUS CYTOPLASM Fig. 11-8-4 Hormone (testosterone) Intracellular receptors EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA mRNA NUCLEUS CYTOPLASM Fig. 11-8-5 Hormone (testosterone) Intracellular receptors EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA mRNA NUCLEUS CYTOPLASM New protein Transduction involves many steps Signal amplification: a few molecules can produce a large cellular response Provide many opportunities for coordination and regulation of the cellular response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Molecules that relay signals are mostly proteins Like falling dominoes, receptors activate another protein, which activates another, and so on, until the protein producing the cellular response is activated At each step, the signal is transduced into a different form, usually a shape change in a protein Carried out via phosphorylation chain reaction Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Signals transmitted by a cascade of protein phosphorylations (adds negative charge to protein & thus changes its conformation) Protein kinases - enzymes that transfer phosphates from ATP to protein, in a process called phosphorylation Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Protein phosphatases - enzymes that remove the phosphates from proteins, a process called dephosphorylation This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-9 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 Pi ATP ADP Active protein kinase 3 PP Inactive protein P ATP P ADP Pi PP Active protein Cellular response Amplify cell’s response Different points at which response can be regulated Specificity of response • Different cells express different collections of proteins e.g. liver cells and neurons Non-protein, water soluble molecules or ions Readily spread through cytoplasm Pathways • G protein coupled receptors • Receptor tyrosine kinases Two most common Cyclic AMP (cAMP) calcium Many signaling molecules trigger formation of cAMP Components of cAMP pathways • G proteins & G protein-coupled receptors • protein kinases Activates protein kinase A, which initiates phosphorylation cascade Further regulation of cell metabolism • G-protein systems that inhibit adenylyl cyclase Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-11 First messenger Adenylyl cyclase G protein G protein-coupled receptor GTP ATP cAMP Second messenger Protein kinase A Cellular responses Calcium ions (Ca2+) - second messenger in many pathways Cells can easily regulate its concentration Signal triggers an increase in cytosolic calcium Other components involved: inositol triphosphate (IP3) diacylglycerol (DAG) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings as additional second messengers Fig. 11-12 EXTRACELLULAR FLUID Plasma membrane Ca2+ pump ATP Mitochondrion Nucleus CYTOSOL Ca2+ pump Endoplasmic reticulum (ER) ATP Key High [Ca2+] Low [Ca2+] Ca2+ pump Fig. 11-13-3 EXTRACELLULAR FLUID Signaling molecule (first messenger) G protein DAG GTP G protein-coupled receptor PIP2 Phospholipase C IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Various proteins activated Ca2+ Ca2+ (second messenger) Cellular responses 1. Describe the nature of a ligand-receptor interaction and how such interactions initiate a signal-transduction system 2. Compare and contrast G protein-coupled receptors, tyrosine kinase receptors, hormone receptors, and ligand-gated ion channels 1. Provide examples for each 3. 4. List two advantages of a multistep signaling cascade in the transduction stage of cell signaling Explain how an original signal molecule can Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 5. Define the term second messenger; and describe the role of these molecules in signaling pathways 1. List two examples 6. Explain why different types of cells may respond differently to the same signal molecule (section 11.4) 1. Provide an example Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings