* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Chapter 11 PowerPoint 2016
Survey
Document related concepts
Protein moonlighting wikipedia , lookup
Extracellular matrix wikipedia , lookup
Cell nucleus wikipedia , lookup
Phosphorylation wikipedia , lookup
Cell membrane wikipedia , lookup
NMDA receptor wikipedia , lookup
Purinergic signalling wikipedia , lookup
Hedgehog signaling pathway wikipedia , lookup
Cytokinesis wikipedia , lookup
Endomembrane system wikipedia , lookup
Tyrosine kinase wikipedia , lookup
Protein phosphorylation wikipedia , lookup
Biochemical cascade wikipedia , lookup
List of types of proteins wikipedia , lookup
G protein–coupled receptor wikipedia , lookup
Transcript
CHAPTER 11: CELL COMMUNICATION Overview: The Cellular Internet • Cell-to-cell communication is essential for multicellular organisms • Biologists have discovered some universal mechanisms of cellular regulation – Evidence of evolution • The combined effects of multiple signals determine cell response – Ex- dilation of blood vessels is controlled by multiple molecules Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Evolution of Cell Signaling • 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 • Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes • The concentration of signaling molecules allows bacteria to detect population density – Quorum sensing (Bonnie Bassler) 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 Cell Signaling Animal cells communicate by: • Direct contact (gap junctions) • Secreting local regulators (growth factors, neurotransmitters) • Long distance (hormones) Local regulators (animals): messenger molecules that travel short distances (this process is not well understood in plants) Examples- growth factors, neurotransmitters 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 Long-distance signaling •In long-distance signaling, plants and animals use chemicals called hormones •Animals- endocrine system •Insulin- regulates sugar levels •Plants- plant growth regulators (factors) •Ethylene- fruit ripening, regulates growth •(Some nerve signals are considered long-distance) Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell (c) Hormonal signaling 3 Stages of Cell Signaling: 1. Reception: Detection of a signal molecule (ligand) coming from outside the cell 2. Transduction: Convert signal to a form that can bring about a cellular response 3. Response: Cellular response to the signal molecule Reception Transduction Response 1. Reception Binding between signal molecule (ligand) + receptor is highly specific. Types of Receptors: a) Plasma membrane receptor water-soluble ligands b) Intracellular receptors (cytoplasm, nucleus) hydrophobic or small ligands Eg. testosterone or nitric oxide (NO) Ligand binds to receptor protein protein changes SHAPE initiates transduction signal Receptors • Three main types of membrane receptors: – G protein-coupled receptors – Tyrosine kinase receptors – Ligand-gated ion channel receptors • Intracellular receptors- found in the cytoplasm or nucleus Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings • A G protein-coupled receptor is a plasma membrane receptor that works with the help of a G protein Signaling-molecule binding site Segment that interacts with G proteins • The G protein acts as an on/off switch: – GDP is bound to G protein, G protein is inactive – GTP is bound to G protein, G protein is active Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-7b G-Protein-Coupled Receptor 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 G protein receptor Inactive enzyme • Tyrosine kinase receptors attach phosphates to tyrosines; Can trigger multiple signal transduction pathways at once 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 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 Cellular response 1 Cellular response 2 • A ligand-gated ion channel receptor acts as a gate when the receptor changes shape • When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 1 Signaling molecule (ligand) Gate closed Ligand-gated ion channel receptor 2 Ions Plasma membrane Gate open Cellular response 3 Gate closed Intracellular Receptors • Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors inside the cell – Examples- steroid and thyroid hormones of animals, NO (nitric oxide) • An activated hormone-receptor complex can act as a transcription factor, turning on specific genes – These receptors also complete the “transduction” step 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. 11-8-4 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA mRNA NUCLEUS CYTOPLASM Fig. 11-8-5 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA mRNA NUCLEUS CYTOPLASM New protein Intracellular Receptors 2. Transduction • Cascades of molecular interactions relay signals from receptors target molecules • Protein kinase: enzyme that phosphorylates and activates proteins at next level – transfer phosphates from ATP to protein, a process called phosphorylation • Phosphorylation cascade: enhance and amplify signal • Protein phosphatases 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 Small Molecules and Ions as Second Messengers • The extracellular signal molecule that binds to the receptor is a pathway’s “first messenger” • Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion • Second messengers participate in pathways initiated by G protein-coupled receptors and receptor tyrosine kinases • Cyclic AMP and calcium ions are common second messengers Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Cyclic AMP • Cyclic AMP (cAMP) is one of the most widely used second messengers • Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal Adenylyl cyclase Phosphodiesterase Pyrophosphate P ATP Pi cAMP Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings AMP Fig. 11-11 First messenger Adenylyl cyclase G protein G protein-coupled receptor GTP ATP cAMP Second messenger Protein kinase A Cellular responses EXTRACELLULAR FLUID Calcium Ions • Calcium ions act as a second messenger in many pathways Ca2+ pump (Ca2+) – More widely used than cAMP • Calcium is an important second messenger because cells can regulate its concentration Plasma membrane ATP Mitochondrion Nucleus CYTOSOL Ca2+ pump Endoplasmic reticulum (ER) ATP Key High [Ca2+] Low [Ca2+] Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Ca2+ pump • A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol – Phospholipase C cleaves the plasma membrane phospholipid PIP2 into DAG and IP3. • Additional second messengers: – Inositol triphosphate (IP3) – Diacylglycerol (DAG) 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 3. Response • Regulate protein synthesis by turning on/off genes in nucleus (gene expression) • Regulate activity of proteins in cytoplasm • Other pathways regulate the activity of enzymes Reception Binding of epinephrine to G protein-coupled receptor (1 molecule) 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 (108 molecules) • Signaling pathways can also affect the physical characteristics of a cell, for example, cell shape RESULTS Wild-type (shmoos) ∆Fus3 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings ∆formin Fig. 11-16b CONCLUSION 1 Mating factor G protein-coupled receptor Shmoo projection forming Formin P Fus3 GTP GDP Phosphorylation cascade 2 Actin subunit P Formin Formin P 4 Fus3 Fus3 P Microfilament 5 3 What a great connection from ch 11 back to ch 6… hint, hint… Fine-Tuning of the Response • Multistep pathways have two important benefits: – Amplifying the signal (and thus the response) – Provide different points at which the response can be regulated • Contributes to the specificity of the response • The response can also ultimately be ended Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Signal Amplification • Enzyme cascades amplify the cell’s response • At each step, the number of activated products is much greater than in the preceding step – Small number of epinephrine molecules can lead to the release of hundreds of millions of glucose molecules from glycogen Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings The Specificity of Cell Signaling and Coordination of the Response • Different kinds of cells have different collections of proteins – allows cells to detect and respond to different signals – same signal can have different effects in cells with different proteins and pathways • Pathway branching and “cross-talk” further help the cell coordinate incoming signals 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. Signaling Efficiency: Scaffolding Proteins and Signaling Complexes • Scaffolding proteins are large relay proteins to which other relay proteins are attached – can increase signal transduction efficiency by grouping together different proteins involved in the same pathway Signaling molecule Plasma membrane Receptor Three different protein kinases Scaffolding protein Termination of the Signal • Inactivation mechanisms are an essential aspect of cell signaling • When signal molecules leave the receptor, the receptor reverts to its inactive state – Each molecular chain in the cascade lasts only a short time • GTPase hydrolyzes GTP • Phosphodiesterase converts cAMP to AMP • Protein phosphatases inactivate kinases Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Concept 11.5: Apoptosis (programmed cell death) integrates multiple cell-signaling pathways • Apoptosis is programmed (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 Blebs Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings • ced-9 = gene Ced-9 protein (active) inhibits Ced-4 activity • Ced-9 = protein • Inhibitory signal (from Ced-9) should look like: 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 • Built-in cell suicide mechanisms are essential to development and maintenance in organisms. Interdigital tissue 1 mm • Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis contributes to some cancers Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings You should now be able to: 1. Describe a ligand-receptor interaction and state how such interactions initiate a signal-transduction system 2. Compare/contrast ligand-gated ion channels, G proteincoupled receptors, & tyrosine kinase receptors 3. List 2 advantages of a multistep pathway in the transduction stage of cell signaling 4. Explain how an original signal molecule can produce a cellular response when it may not even enter the target cell 5. Define the term second messenger; briefly describe the role of these molecules in signaling pathways 6. Explain why different types of cells may respond differently to the same signal molecule 7. Describe the role of apoptosis in normal development and degenerative disease in vertebrates