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Fig. 11-1 Chapter 11: Cell Communication 11.1 Involved in regulation within living organisms. • How cells detect, process, and respond to chemical signals from other cells • Signal transduction pathway =process by which a signal on a cell’s surface is converted to a specific cellular response. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 1. Local Regulators-substance that influences nearby cells a. Paracrine signaling: one signal cells sends out message to many nearby cells. Ex. growth factors: stimulate cells to grow and multiply b. Synaptic signaling: neurotransmitter crosses synapse and triggers nerve impulse Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-5ab Local signaling Electrical signal along nerve cell triggers release of neurotransmitter Target cell Secreting cell Local regulator diffuses through extracellular fluid (a) Paracrine signaling Neurotransmitter diffuses across synapse Secretory vesicle Target cell is stimulated (b) Synaptic signaling c. Identification of Mates 1. Yeast mating types = a (secretes a factor) and α (secrete α factor) 2. Factors bind to receptors on opposite mating type 3. Cells grow towards each other and fuse 4. Result = a/α cell with all of the genes of both mating types 2. Hormonal Signaling: greater distance a. animals: hormones released from glands travel through blood stream b. plants: hormones may diffuse through cells or air as a gas (ethylene gas) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 3. Direct contact: a. Dissolved substances move through cytosol from cell to cell through openings (plasmodesmata, gap junctions) b. Direct contact between molecules on cell surfacesimportant in embryonic development The Three Stages of Cell Signaling • Earl W. Sutherland (Nobel Prize in 1971) discovered how the hormone epinephrine acts on cells 1. Reception: chemical signal detected when it binds to a cellular protein on surface, changing receptor protein in some way 2. Transduction: converts signal into a form that can bring about a cellular response (usually occurs in a series of steps-signal transduction pathway) 3. Response- transduced signal triggers a response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 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 11.2 Signal Reception and the Initiation of Transduction • Signal molecule or ligand binds to receptor protein causing it to change conformation. – A shape change in a receptor is often the initial transduction of the signal – Very specific, like lock and key or enzyme/substrate Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings I. Receptors in the Plasma Membrane 1. G protein-coupled receptor: plasma membrane receptor that works with the help of a G protein a. Anatomy: 1. Receptor: seven α-helices spanning the membrane 2. The G protein acts as an on/off switch: 3. GUANINE nucleotides: GDP is bound=inactive GTP is bound =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 Receptors in the Plasma Membrane b. Physiology: 1. Ligand binds to receptor 2. Receptor conformation changes 3. Receptor binds to an inactive G protein causing GDP to be displaced by GTP. 4. Activated G protein binds to another protein (usually and enzyme) and changes its activity 5. GTPase enzyme hydrolyzes GTP to GDP and the G protein is inactive Up to 60% of all medicines work because of their effects on G proteins! Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-7b Plasma membrane G protein-coupled receptor Activated receptor Signaling molecule GDP CYTOPLASM GDP Enzyme G protein (inactive) GTP 2 1 Activated enzyme GTP GDP Pi Cellular response 3 4 Inactive enzyme 2. Tyrosine-Kinase Receptors a. Tyrosine-Kinase catalyzes the transfer of phosphate groups from ATP to the amino acid tyrosine on a substrate protein. b. How it works: 1. Before signal molecule binds, receptor = individual polypeptides 2. Ligand binding causes the two polypeptides to combine 3. Tyrosine-Kinases on each polypeptide activated 4. Each phosphorylates the tyrosines in the tail of the other 5. The receptors are now activated and they turn on active relay proteins 6. The relay proteins trigger many different transduction pathways. Abnormal tryosine-kinase receptors that aggregate without a ligand cause some kinds of cancer! 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 3. Ion Channel Receptors a. Ligand-gated ion channel =protein pores in the membrane b. Open or close in response to a chemical signal c. Allows or blocks flow of specific ions, such as Na+ or Ca2+ d. Important to nerve impulse transition Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-7d 1 Signaling molecule (ligand) Gate closed Ligand-gated ion channel receptor 2 Ions Plasma membrane Gate open Cellular response 3 Gate closed 4. Intracellular Receptors a. Some receptor proteins are found in the cytosol or nucleus b. Chemical messengers can readily cross the target cell’s membrane c. Bind to receptors which turn on genes d. ex. steroid hormones (lipids) and small gaseous molecules (NO2) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-8-1 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein DNA NUCLEUS CYTOPLASM Fig. 11-8-2 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA NUCLEUS CYTOPLASM Fig. 11-8-3 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA NUCLEUS CYTOPLASM Fig. 11-8-5 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA mRNA NUCLEUS CYTOPLASM New protein 11.3. Signal Transduction Pathway: like falling dominoes 1. Multistep pathways which relay signals from receptors to cell responses 2. Benefit = amplification 3. Relies on protein conformation changes by phosphorylation by protein kinases 4. Signal transmitted by a cascade of protein phosphorylations. 5. The effects of protein kinases are rapidly reversed by protein phosphates (dephosphorylation) 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 Second Messengers 1. Small, non-protein, water-soluble molecules or ions that spread throughout a cell by diffusion (Ca2+ and Cyclic Amp) 2. Cyclic Amp (adenosine monophosphate) a. extracellular signal causes adenylyl cyclase to convert ATP to cAMP. b. cAMP then activates a protein kinase which causes a cascade of reactions Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-10 Adenylyl cyclase Phosphodiesterase Pyrophosphate P ATP Pi cAMP AMP Fig. 11-11 First messenger Adenylyl cyclase G protein G protein-coupled receptor GTP ATP cAMP Second messenger Protein kinase A Cellular responses 3. Calcium Ions and Inositol Triphosphate (IP3) a. Calcium (Ca2+) is an important second messenger because cells can regulate its concentration b. Ca2+ ions stored in the ER Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 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 c. Process: 1. Signal molecule binds to a receptor 2. Phospholipase C activated 3. Cleaves special phospholipid (PIP2) into the second messengers DAG (diacylglycerol) and IP3 4. IP3 diffuses through cytosol and binds to gated channel 5. Ca2+ flows out of ER 6. Ca2+activate next protein in signal pathway Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 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 11.4. Cellular Responses to Signals 1. May regulate activities in the cytoplasm a. Enzyme activity b. Rearrangement of the cytoskeleton 2. May regulate transcription a. Activate transcription factors b. Turn on specific genes Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-14 Growth factor Reception Receptor Phosphorylatio n cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor P Response DNA Gene NUCLEUS mRNA Fine-Tuning of the Response • Multistep pathways have two important benefits: – Amplifying the signal (and thus the response) – Contributing to the specificity of the response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Amplification 1. Elaborate enzyme cascades amplify the cell’s response to a signal 2. At each step in the cascade, the number of activated products is greater Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Specificity 1. Different kinds of cells have different proteins! 2. Response to a signal will vary based on receptors, relay molecules, and proteins needed to carry out the response. 3. Same signal molecule can cause different responses in different cells. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-17 Signaling molecule 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. 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 (programmed cell death) integrates multiple cell-signaling pathways • Apoptosis is programmed or controlled cell suicide • A cell is chopped and packaged into vesicles that are digested by scavenger cells • Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-19 2 µm Fig. 11-20 Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Ced-4 Ced-3 Receptor for deathsignaling molecule Inactive proteins (a) No death signal Ced-9 (inactive) Cell forms blebs Deathsignaling molecule Active Active Ced-4 Ced-3 Activation cascade (b) Death signal Other proteases Nucleases Apoptotic Pathways and the Signals That Trigger Them • Caspases are the main proteases (enzymes that cut up proteins) that carry out apoptosis • Apoptosis can be triggered by: – An extracellular death-signaling ligand – DNA damage in the nucleus – Protein misfolding in the endoplasmic reticulum Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings • Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals • Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-21 Interdigital tissue 1 mm