Transcript Cell A.
Chapter 11 Cell communication How cells detect, process, and respond to chemical signals send from other cells or from changes in the physical environment ? • Overview: The Cellular Internet • Cell-to-cell communication – Is absolutely essential for multicellular organisms – External signals are converted into responses within the cell Ex. Yeast cells --- Identify their mates by cell signaling Cell signaling evolved early in the history of life Saccharomyces cerevisiae “yeast” --- identify their mates by chemical signaling 1 Exchange of mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type. 2 Mating. Binding of the factors to receptors induces changes in the cells that lead to their fusion. factor Receptor a Yeast cell, factor Yeast cell, mating type a mating type a Two sex,(mating type) Without actually entering the cells, the receptor-bound molecules of the two mating factors cause the cells to grow toward each other and bring about other cellullar changes. 3 New a/ cell. The nucleus of the fused cell includes all the genes from the a and a cells. a/ Figure 11.2 The process by which a signal on a cell’s surface is converted into a specific cellular response is a series of steps --- called a signal-transduction pathway • Signal transduction pathways – Convert signals on a cell’s surface into cellular responses – Are similar in microbes and mammals, suggesting an early origin – Cells in a multicellular organism --- communicate via chemical messengers • Animal and plant cells – Have cell junctions that directly connect the cytoplasm of adjacent cells Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells Figure 11.3 (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes. • In local signaling, animal cells – May communicate via direct contact Figure 11.3 (b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces. • In other cases, animal cells – Communicate using local regulators Paracrine signaling: --- the transmitting cell secretes molecules of a local regulator a substance that influences cells in the vicinity. Growth factor neurotransmitter Local signaling Target cell Secretory vesicle Figure 11.4 A B Local regulator diffuses through extracellular fluid (a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid. Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Target cell is stimulated (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. • In long-distance signaling – Both plants and animals use hormones * Endocrine signaling: (animal cells) Long-distance signaling Blood vessel Endocrine cell --- specialized cells release hormone molecules into vessels of the circulatory system. * In plants, hormones sometimes travel in vessels Hormone travels in bloodstream to target cells but more often reach their targets by moving through cells or by diffusion through the air as a gas. Target cell (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells. Figure 11.4 C The plant hormone ethylene, a gas that promotes fruit ripening and helps regulate growth. (C2H4) What happens when a cell encounters a signal ? The signal must be recognized by a specific receptor molecule, and the information it carries must be changed into another form-transduced-inside the cell before the cell can respond. The three stages of cell signaling are reception, transduction, response Earl W. Sutherland (Nobel Prize in 1971) How the animal hormone epinephrine stimulates breakdown of the storage polysaccharide glycogen within liver and skeletal muscle cells. Glycolysis: Glycogen Glucose-1-phosphate Glucose-6-phosphate glucose Epinephrine Enzyme: Glycogen phosphorylase 1. When epinephrine was added to a Test-tube mixture containing the phosphorylase and its substrate, glycogen no depolymerization occurred 2. Epinephrine could activate glycogen phosphorylase only when it was added to a solution containing intact cells. Glycogen Glucose-1-phosphate Glucose-6-phosphate glucose 1. Epinephrine does not interact directly with the enzyme responsible for glycogen breakdown. 2. The plasma membrane is somehow involved in transmitting the epinephrine signal. Relay molecules 1. Catalysis by an enzyme 2. Rearrangement of the cytoskeleton 3. Activation of specific genes in the nucleus Signal reception and the initiation of transduction yeast cell only “heard” the signals by its prospective mates, a cells. The signal receptor is the identity tag on the target cell. A signal molecule binds to a receptor protein, causing the protein to change shape. * The term for a small molecule that specifically binds to a larger one ligand Key & lock receptor Conformational change receptor activation Most signal receptors are plasma membrane proteins Receptor transmits information from the extracellular environment to the inside of the cell by changing shape or aggregating when a specific ligand binds to it. Three major types of membrane receptors: 1. G-protein-linked receptors 2. tyrosin-kinase receptors 3. ion-channel receptors 1. G-protein-linked receptors --- a plasma membrane receptor --- works with the help of a protein called a G protein --- vary in their binding sites for recognizing signal molecules and for recognizing different G proteins G-protein-linked receptor: --- involved in diseases. cholera 霍亂 pertussis 百日咳 --- widespread and diverse in functions. * mouse embryogenesis * sensory reception (vision and smell) 視覺 Signal-binding site G protein: GDP bound --- inactive GTP bound --- active 嗅覺 G-protein-linked Receptor Plasma Membrane Activated Receptor Signal molecule GDP CYTOPLASM Segment that interacts with G proteins G-protein (inactive) GDP Enzyme 1. GTP 2. Activated enzyme Figure 11.7 GTP GDP Pi 3. Cellular response Figure 11.7 4. Inctivate enzyme 2. Tyrosine-Kinase Receptors ( have enzymatic activity 酵素活性: tyrosin kinase) --- a type of receptor specialized for triggering more than one signal-transduction pathway at once. Signal-binding sitea Signal molecule Signal molecule Helix in the Membrane Tyr Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins (inactive monomers) CYTOPLASM Tyr Dimer 1. Polypeptide aggregation 2. Phosphorylation of the Activated relay proteins Tyr P Tyr P Tyr Tyr P Tyr P Tyr P Tyr Tyr P Tyr Tyr Tyr Tyr 6 ATP Activated tyrosinekinase regions (unphosphorylated dimer) 6 ADP Fully activated receptor tyrosine-kinase (phosphorylated dimer) P Tyr P Tyr P Tyr Tyr P Tyr P Tyr P Inactive relay proteins receptor Cellular response 1 Cellular response 2 The ability of a single ligand-binding event to trigger so many pathways is a key difference between these receptors and G-protein-linked receptors. Ligand independent activation of tyrosin-kinase receptor Mutation (突變) Signal molecule (ligand) Gate closed Ions Ion-channel receptors: Ligand-gated ion channels Ligand-gated ion channel receptor Plasma Membrane * Nervous system Gate open Cellular response Gate close Figure 11.7 Not all signal receptors are membrane proteins !! Intracellular receptors : --- in the cytosol or nucleus of target cells. --- * hydrophobic : steroid hormones tyroid hormones ex. Testosterone (one steroid hormone) --- secreted from testis * small molecules : nitric oxide (NO) Activated testosterone receptor Transcription factors In nucleus: ex, estrogen receptors transcription translation Signal-transduction pathways Relay molecules --- multistep pathway --- signal amplification 1. Catalysis by an enzyme 2. Rearrangement of the cytoskeleton 3. Activation of specific genes in the nucleus Protein phosphorylation Conformational change Protein phosphorylation: --- a widespread cellular mechanism for regulating protein activity. Protein kinase: (磷酸激酶) - an enzyme that transfers phosphate Protein phosphatase: (去磷酸酶) - an enzyme that remove phosphate groups from proteins. groups from ATP to a protein. ATP ADP kinase A phosphatase inactive Pi A P active Protein kinase: tyrosin kinase serine/threonine kinase 1% A phosphorylation cascade Not all components of signal-transduction pathway are proteins !! Many signaling pathways also involve small, nonprotein, water-soluble molecules or ions Second messengers * Spread by “diffusion” * Participate in pathways initiated by both G-protein-linked receptors and tyrosin-kinase receptors. * Including cyclic AMP and calcium ions (Ca2+). Cyclic AMP Cyclic adenosine monophosphate; cyclic AMP; cAMP NH2 N N O O O N N – O P O P O P O Ch2 O O O Figure 11.9 N N O Pyrophosphate P Pi O CH2 Phoshodiesterase O OH Cyclic AMP N N O HO P O CH2 O O P O N N N N Adenylyl cyclase O OH OH ATP NH2 NH2 O H2O OH OH AMP • Many G-proteins – Trigger the formation of cAMP, which then acts as a second messenger in cellular pathways First messenger (signal molecule such as epinephrine) G protein G-protein-linked receptor Adenylyl cyclase * Cholera --- Vibrio cholerae --- produce a toxin, which modifies a G protein GTP ATP cAMP Protein kinase A Cellular responses Figure 11.10 * Some are inhibitory G protein which inhibit adenylyl cyclase. involved in regulating salt and water secretion. Neurotransmitters Growth factors hormones Cytosolic concentration of calcium ions (Ca2+) Muscle cell contraction secretion Cell division Ca2+ More widely used than cAMP as a second messenger Ca2+ concentration in the cytosol is normally much lower than the concentration outside the cell. 10,000X Figure 11.11 EXTRACELLULAR FLUID ATP Plasma membrane Ca2+ pump Mitochondrion * Diacylglycerol (DAG) * Inositol trisphosphate Nucleus (IP3) CYTOSOL Ca2+ pump ATP Ca2+ Endoplasmic reticulum (ER) pump Key High [Ca2+] Low [Ca2+] * Calcium and IP3 in signaling pathways. 1 A signal molecule binds to a receptor, leading to activation of phospholipase C. EXTRACELLULAR FLUID 2 3 DAG functions as a second messenger in other pathways. Phospholipase C cleaves a plasma membrane phospholipid called PIP2 into DAG and IP3. Signal molecule (first messenger) G protein DAG GTP PIP2 G-protein-linked receptor Phospholipase C IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) Various proteins activated Ca2+ Cellular response Ca2+ (second messenger) 4 IP3 quickly diffuses through the cytosol and binds to an IP3– gated calcium channel in the ER membrane, causing it to open. Figure 11.12 5 Calcium ions flow out of the ER (down their concentration gradient), raising the Ca2+ level in the cytosol. 6 The calcium ions activate the next protein in one or more signaling pathways. Concept 11.4 Response: cell signaling leads to regulation of cytoplasmic activities or transcription Growth factor Reception Binding of epinephrine to G-protein-linked receptor (1 molecule) Reception Receptor Transduction Inactive G protein Active G protein (102 molecules) Phosphorylation cascade Transduction Inactive adenylyl cyclase cytoplasmic response Active adenylyl cyclase (102) nucleus response CYTOPLASM 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) Inactive transcription factor Active transcription factor P DNA Gene Response Glycogen Glucose-1-phosphate (108 molecules) Response NUCLEUS mRNA Why are there often so many steps between a signaling event at the cell surface and the cell’s response ? Two important benefits: 1. Signal amplification 2. The specificity of response Reception Binding of epinephrine to G-protein-linked receptor (1 molecule) Transduction Inactive G protein Active G protein (102 molecules) * At each catalytic step in the cascade, the number of activated products is much greater than in the preceding step. 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 Figure 11.13 Glucose-1-phosphate (108 molecules) Signaling pathways with a multiplicity of steps have two important benefits: 1. amplify the signal 2. contribute to the specificity of response The specificity of cell signaling epinephrine Liver cell Glycogen breakdown heart cell contraction The response of a particular cell to a signal depends on its particular collection of signal receptor proteins, relay proteins, and proteins needed to carry out the response. Signal molecule Receptor Relay molecules Cell A. Pathway leads to a single response Response 1 Cell C. Cross-talk occurs between two pathways Response 2 3 Cell B. Pathway branches, leading to two responses Cell D. Different receptor leads to a different response Activation or inhibition Response 4 Figure 11.15 Response Response 5 Signaling Efficiency: Scaffolding Proteins and Signaling Complexes • Scaffolding proteins – Can increase the signal transduction efficiency Signal molecule Plasma membrane Receptor Scaffolding protein Figure 11.16 Three different protein kinases A key to a cell’s continuing receptiveness to regulation is the reversibility of the changes that signals produce. Termination of the Signal How ? • Signal response is terminated quickly – By the reversal of ligand binding – The relay molecules return to their inactive forms.