Cell-Cell Interactions Cont. Part 1
Cell-Cell Interactions Cont. Part 1 200001
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This 13 page Class Notes was uploaded by Olivia Sutton on Monday March 7, 2016. The Class Notes belongs to 200001 at Boston College taught by Danielle Taghian in Spring 2016. Since its upload, it has received 16 views. For similar materials see Molecules and Cells in Biology at Boston College.
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Date Created: 03/07/16
February 26, 2016 Lecture 10: Cell-Cell Interactions Part 1 How Do Distant Cells Communicate? Intercellular connections are the basis of multicellularity, which is the physical connection between cells (either direct or indirect via the ECM) Long Distance signals o Coordinate activities of cells, tissues, and organisms in different parts of a multicellular organism Hormones are information carrying molecules that are: o Secreted from a cell o Circulates in the body o Acts on target cells far from signaling cell Hormones are long distance messengers o Are small and circulated in minute concentratons, but have a very LARGE impact on the whole organism The function & chemical structure of plant and animal hormones vary widely Different hormones vary greatly in their hydrophilicity or lipophicility o If you have a very hydrophobic hormone, typically these hormones can pass through the membrane if they are small Ligand: chemical message that gets received on the receptor of another cell type If the hormone is non steroidal based or larger, the message will have to be received on a plasma membrane of another cell Signal Reception Receptors: found in cell membrane or in cytosol Hormones and other cell-cell signals bind to receptors Different cells have different receptors on them, which dictates the response to a specific hormone Binding of a hormone changes that receptor’s shape (conformational change) and this causes it to be activated and information to be relayed Most signal receptors are located in the plasma membrane, but signal receptors that bind to steroid hormones are located inside the cell The goal is to make changes in the nucleus of the cell Different Types of Receptors Hormone receptors G-protein coupled receptors Receptor Tyrosine Kinases Ligand-gated ion channels Lipid-soluable steroid hormones Bind to receptors inside the cell Trigger a change in the cell’s activity directly Hormone-receptor complexes binds to DNA and can induce changes in gene expression Steroid hormones are sent into the cell in high concentrations, so the receptor’s chance of binding to the hormone is high February 29, 2016 Lecture 10: Cell: Cell Interactions Part 2 Every cell in the body has the same nucleus The only difference among cells is the gene expressions involved The only cells that are susceptible to changes in gene expression are ones that have receptors Signal Processing Hormones that cannot diffuse across the plasma membrane rely on signal transduction pathways o Converts the extracellular hormone signal to a new intracellular signal o Signal transduction occurs on the plasma membrane o Amplification occurs inside When a hormone arrives at the cell surface, the signal gets amplified Signal transduction pathways involve: o G proteins: trigger the production of intracellular messengers o Enzyme-linked receptor: triggers activation of proteins in the cell The receptor is a transmembrane protein Molecules get activated and begin to activate other molecules, eliciting a change in cell activity G Proteins Are peripheral membrane proteins located inside the cell that are closely associated with the transmembrane signal Are activated when they bind to GTP and deactivated when GTP is hydrolyzed to GDP (can bind to either one of those) GPCR: G-protein coupled receptor; always has a G protein associated with them on the inside of the lipid bilayer G-protein attached undergoes a change; which happens when the protein switches out the molecule GTP: has three phosphate groups attached to them o When G proteins are bound to this, nothing happens GDP: has two phosphate groups attached When a hormone signal binds to a G-protein linked receptor, another protein kicks of the attached GDP and activates the GTP protein The purpose of every shape change of a protein is to act as a docking site for other proteins Steps: o Hormone binds receptor o Conformational change activates G protein o G protein binds GTP o Activated G protein activates membrane-assondated enzyme which is then able to release a 2 messenger -> rapid diffusion in cell Phosphorylation: when a protein takes a phosphate group Second Messengers Adenylyl cyclase: takes ATP and converts it to form a second messenger Activated because GTP is bound to it (causes it to changes shape) Cyclic AMP can stimulate the activity of protein kinase A and other proteins Phospholipase C cleaves the IP3 molecule off of the phospholipid and converts it into diasoglycerol (sends its own signal) All of this happens near the membrane IP3 and Ca2+: 2 ndmessengers IP3: inositol triphosphate; a soluble signal that is made by the hydrolysis of PIP2 (a membrane phospholipid) Ca2+ is released from the SER (smooth endoplasmic reticulum) by the binding of IP3 to the SER channel protein nd A signal hormone can stimulate the production of many 2 messengers RTKs Receptor tyrosine kinases: do not have large G proteins linked to them o Kinase: it is able to add other phosphate groups to it Classified as enzyme linked Have the ability to phosphorylate proteins Adds phosphate groups to tyrosines There are two pieces to the receptor, so they collide in order for the signal to be transmitted o The hormone binds to one half of the receptor and the other half is attracted to it When a signal is received, the receptor automatically phosphorylates Ras: is a G protein that only has one subunit to it instead of three o Can bind GDP when inactive and bind GTP when it is active o Kicks off the GDP Bridging proteins are able to stick to the receptor and Ras can come in since the receptor is now a docking site Ras and G proteins are not kinases!! Triggering a Phosphorylation Cascade Activated receptors->phosphorylate and activate other enzymes- >activate more enzymes, and so on, creating a phosphorylation cascade Signal transduction converts an easily transmitted extracellular message into a greatly amplified intracellular message that carries information throughout the cell and induces a cellular response Phosphate comes from an ATP molecule in order to phosphorylate that tail of the tyrosine Phosphate group attracts other proteins Bridging proteins come from the attraction to tyrosine; it is activated because it has GTP Every other protein in the cascade is a kinase Each kinase can only phosphorylate its intended target, making it highly selective Tyrosines internalizes once the process begins Signal Responses: What is the Ultimate Response to the Messages Carried by Hormones Gene Expression: a change in which genes are being expressed in the cell Activation/Deactivation of a particular target protein that already exists in the cell Bottom line: signal transduction dramatically changes the activity of the target cell Signal Deactivation G proteins convert GTP back to GDP o Extracellular signal is no longer produced Phosphatases—enzymes that remove phosphate groups from proteins A phosphate falls off of the GTP to turn it back to GDP o The phosphate is EVERYTHING!! These mechanisms allow the cell to remain sensitive to small changes in the concentration of hormones or in the number and activity of signal receptors Removing phosphates doesn’t always results in deactivation Which of the following is NOT in the plasma membrane? Steroid hormone receptor: in the cytosol G protein coupled receptor: just hanging out Receptor tyrosine kinase: located on the cell membrane Ligand gated ion channel: located on the membrane of the smooth ER Crosstalk: interactions between signaling pathways Crosstalk: integrates diverse signals a cell receives Elements/products from one pathway may affect another pathway, ultimately affecting the overall cell response o Cell response can be reduced when one pathway inhibits another How signaling pathways intersect There are multiple points where the cell can regulate the flow of info, allowing the cell to respond appropriately to many simultaneous
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