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Transcript
Overview: The Cellular Internet • Cell-to-cell communication is essential for organisms • Biologists have discovered some universal strategies and mechanisms of cellular regulation • Response is determined by combined effects of multiple signals Yeast Mating-a classic system 1 Exchange of mating factors factor Receptor a a factor Yeast cell, mating type a 2 Mating Yeast cell, mating type a An example of cell signalling 3 New a/ cell a/ • Yeast Mating System Exemplifies Cell Communication • Aka Signal Transduction • Simple but all the key features are present • Reception, Transduction, Response • 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 in Vibrio fischerii When cells are touching signalling is easy Plasma membranes Gap junctions between animal cells (a) Cell junctions (b) Cell-cell recognition Plasmodesmata between plant cells • In many other cases, cells must share information with cells they are not touching • They use (1) local regulators, messenger molecules that travel only short distances • And (2) chemicals called hormones for longdistance signaling Local signaling in animals is either paracrine or synaptic 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 Both are short-range but synaptic signaling occurs only in the nervous system Long-distance signaling usually involves different organs communicating Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell (2) Hormonal signaling The messenger molecules are called hormones There are three stages in cell signaling 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 Reception Transduction Response RECEPTION TRANSDUCTION RESPONSE • The binding between a signal molecule (ligand) and receptor is highly specific • A shape change in a receptor is often the initial transduction of the signal • Most signal receptors are plasma membrane proteins • 3 examples from many possible Reception- Example I • A G protein-coupled receptor is a plasma membrane receptor that works with the help of a G protein • The G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive • GTP/GDP are chemically very similar to ATP/ADP but contain Guanine not Adenine Mechanism of G protein coupled reception 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 The relay protein is called a “G Protein” Inactive enzyme Reception- Example II • Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines • Has intra- and extracellular domains, also membrane domain • A receptor tyrosine kinase can trigger multiple signal transduction pathways at once • Kinase is an enzyme that attaches a phosphate to a substrate 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 Reception- Example III • 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 Ligandgated ion channel 1 Signaling molecule (ligand) Gate closed Ligand-gated ion channel receptor 2 Ions Plasma membrane Gate open Cellular response 3 Gate closed Reception Signal Binding of epinephrine to G protein-coupled receptor (1 molecule) Transduction: Transduction an example of a key type of transduction pathway and response An example of a response (Do not memorize this cascade) Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) This type of signal transduction pathway is called a cascade 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) Cyclic AMP is the key inside the cell. Adenylyl cyclase Phosphodiesterase Pyrophosphate P ATP Pi cAMP Cyclic AMP is the “second messenger” AMP Ethylene Response in plants Identify: Reception, Transduction, Response