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Lec 37

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University of Lethbridge
BIOL 1010
Igor Kovalchuk

Signal Transduction Lecture 37 Communication between mating yeast cells  Cells of the yeast use chemicals signaling to identify type and initiate the mating process.  1. Cells of a mating type “a” release “a”-factor, which bonds to receptors on nearby cells of mating type alpha. Alpha cells release alpha factor, which binds to specific receptors on “a” cells.  (Note: factors are peptides about 12 amino acids in length.)  2. Binding of the factors to receptors induces changed in the cells that lead to their fsion, or mating.  3. The resulting “a”/alpha cell combines in its nucleues all the genes from the “a” and alpha cellls. Communicating cells may be close together or far apart  A chemical signal that communicates between two nearby cells is called a local regulator  Animals-two types of local signaling: o In paracrine signaling one cell secretes signal in extracellular fluid and signal acts on nearby target cells  Eg. Growth factors-stimulate cells to divide and grow o In synaptic signaling- a nerve cell releases a signal (eg. Neurotransmitter) into a synapse, the narrow space between the transmitting cell and a target cell, such as a nerve cell and muscle cell.  A chemical signal which communicates between two cells some distance apart is called a hormone o In plants- ethylene o Animals- insulin and others  Distinction between local regulators and hormones if for convience  A particular chemical signal may act both as local regulator and as a hormone o Eg. Insulin  Cells may also communicate by direct contact Overview of cell signaling  From the perspective of the cell receiving the message, cell signaling can be divided into three stages: o Signal reception o Signal transduction o Cellular response Three stages of signaling  Reception- Signal binds to a specific cellular protein called a receptor, which is often located on the surface of the cell  Transduction- binding of a signal changes the receptor in some way, usually a change in conformation or shape  The change in receptor initiates a process of converting the signal into specific cellular response; this process is called signal transduction  The transduction system may have one or many steps  Response- the transduction system triggers a specific cellular response  The response may be almost any cellular activity, such as activation of enzyme or altered gene expression Signal reception and initiation of transduction  A chemical signal binds to a specific receptor causing the protein to change shape  The signal behaves as a ligand, a term for a small molecule that bonds to another, larger molecule  Binding of the ligand induces: o Alteration in receptor conformation or shape, this may lead to activation of the receptor which enables it to interact with another molecule o Aggregation of receptor complexes Most signal receptors are membrane proteins  There are 3 families of plasma-membrane receptors: o G-linked protein receptors o Tyrosine kinase receptors o Ion channel receptors G-linked proteins receptors  Structure of G-linked protein receptors is characterized by a single polypeptide chain that is threaded back and forth through the plasma membrane  The receptor propagates a signal by interacting with a variety of proteins on the cytoplasmic side of the membrane  Called G-proteins, so named because they bind guanine nucleotides, GTP and GDP  The function of G=protein is influenced by the nt to which it is bound: o G-proteins bound to GDP are inactive o G-proteins bound to GTP are active A functioning of a G-protein-linked receptor  A) In the absence of the extracellular signal molecule, all three proteins are inactive form  The inactive G protein has a GDP molecule bound to it  B) Binding of the signal changes the receptors shape in which a way that it binds and activates the G protein  A Molecule of GTP replaces the GDP on the G protein  The active G protein binds to and activates the enzyme, which triggers the next step in the pathway leading to the cell’s responses  C) The G protein that catalyzes the hydrolysis oft its GTP and dissociates from the enzyme, becoming available for reuse  All three proteins remain attached to the plasma membrane The structure and function of a tyrosine-kinase receptor  (A) In the absence of specific signal molecules, tkr exist as signal polypeptides in the plasma membrane  The extracellular portion has signal-binding site responsible for the receptor’s tyrosine-kinase activity  (B) Signal molecules attach tot their binding sites and two polypeptides aggregate, forming a dimer.  Using phosphate groups from ATP, the tyrosine-kinase region of each polypeptide phosphorylates the tyrosine’s on the other polypeptide  In other words, the dimer is both an enzyme and its own substrate  Active receptor protein can bind specific intracellular proteins, which attach to a particular phosphorylated tyrosine’s and are themselves activated  Each can then initiate a signal-transduction pathway leading to a specific cellular response  TKRs activate several different signal- transduction pathways at once and regulate cell reproduction  Inappropriate activation of these receptors can lead uncontrolled cell growth- cancer. Ion-channel receptors  Some chemical signals bind to ligand-gated ion channels  These are protein pores in the membrane that open and close in response to ligand binding, allowing blocking of flow of specific ions ( Na+, Ca2+) o An example of the ion-gated channel would be the binding to neurotransmitter to the neuron, allowing the inward of Na+ that leads to depolarization of the neuron and the propagation of a nervous impulse to adjacent cells A Ligand-gated ion-channel receptor.  This signal receptors is a trans membrane protein in the plasma membrane that opens to allow the flow of a specific kind of ion across the membrane when a specific signal molecule binds to the extracellular side of the protein Not all receptors are located on the plasma membrane  Some are proteins located in the cytoplasm or nucleus of target cells  In order for a chemical to bind these intracellular receptors, the signal molecule must be able to pass through the plasma membrane  Examples of signals binding to intracellular receptors include: o Nitric oxide o S
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