Why Do Cells Communicate? Regulation Cells need to control cellular processes In multicellular organism, cells signaling pathways coordinate the activities within individual cells that support the function of the organism as a whole Environmental Stimuli Cells need to be able to respond to signals from their environment Single celled organisms use cell signaling pathways to respond to their environment Cell Signaling (C.S.) Is a relatively new topic in Bio/AP Bio Appears to answer many questions in medicine Especially since signal transmission within and between cells mediated gene expression (causes genes to turn on and off) Stages of Cell Signaling 1. Reception- receiving the signal 2. Transduction- passing on the signal 3. Response- cellular changes because of the signal Reception The target cell s detection of a signal coming from outside the cell May Occur by: Direct connect Through signal molecules
Direct Connect When molecules can flow directly from cell to cell without crossing membranes Plants- plasmodesmata Animals- gap junctions Reception may also occur by cell surface molecules that project from the surface and touch another cell Example -Interaction between cells of the immune system Signal Molecules The actual chemical signal that travels from cell to cell Often water soluble b/c of polarity Usually too large to travel through membranes Behave as ligands : a smaller molecule that binds to a large one Signal molecules can be local regulators that target cells within the vicinity of the emitting cell (neurotransmitters), or they can travel long distances to target cells of another type (hormones) Receptor Molecules Usually made of protein: highly specific 3-D shape to only bind with their specific signal molecule (ligand) Change shape when bind to a signal molecule, initiating transduction (Conformation change) Transmits information from the exterior to the interior of a cell Receptor Mechanisms 1. G-Protein linked 2. Tyrosine-Kinase 3. Ion Channels 4. Interacellular
G-Protein Linked Plasma membrane receptor Works with G-Protein an interacellular protein w/ GDP & GTP GDP & GTP act as a switch GDP-inactive / GTP- active When active (GTP), the protein binds to another protein (enzyme0 and alters its activation (turn it on) Active site is only temporary G-Protein Process: How epinephrine triggers the conversion of glycogen into glucose G-Protein Linked Receptors 1.G-protein w/out ligand (no activation) 2.Ligand or epinephrine attaches (reception) 3.Activates subunit which moves w/ GTP across the membrane 4.Attaches to enzyme (Adenylyl cyclase) 5.This converts ATP->cAMP 6.cAMP attaches to regulator side on a protein kinase 7.Protein kinase releases the catalic side which converts glycogen->glucose 8.Release ligand to stop Very widespread and diverse in functions Ex-vision, smell, blood vessels development Many diseases work by affecting g-protein linked receptors Ex-Whooping cough, botulism, cholera, some cancers Up to 60% of all medicines exert their effectd through g-protein linked receptors Tyrosine-Kinase Receptors Extends through the cell membrane Intracellular part functions as a kinase, which transfers Pi from ATP to tyrosine on a substance protein Unlike G-proteins that activate only one pathway, these often activate several different pathways at once, helping regulate complicated functions such as cell division
Tyrosine-Kinase Receptor Mechanism 1.Ligand binding- causes two receptor molecules to aggregate (Ex. Growth hormone) 2.Activation of tyrosine-kinase parts in cytoplasm 3.Phosphorylation of tyrosines by ATP (sets off several pathways) Intracellular Proteins Become activated and case the cellular response Ion Channel Receptors Protein pores in the membrane that open or close in response to chemical signals Allow or block the flow of ions such as Na+ or Ca2+ Activated by a ligand on the extracellular side Causes a change in ion concentration inside the cell Ex-Nervous system signals Intracellular Signals Proteins located in the cytoplasm or nucleus that receive a signal that CAN pass through the cell membrane (small/nonpolar) Ex-Steroids (hormones) No-nitric oxide Activated protein turns on genes in nucleus Most signals never enter a cell, the signal is received at the membrane and passed on Exception-intracellular receptors Signal-Transduction Pathways The further amplification and movement of a signal in the cytoplasm to cause a cellular response Often has multiple steps using relay proteins such as protein kinases Protein Phosphorylation The addition of Pi to a protein which activates the protein
Protein Kinase Secondary Messengers General name for any enzyme that transfers Pi from ATP to a protein Amplification Often works in a cascade w/ each being able to activate several molecules Result-from one signal, many molecules can be activated Signaling pathways w/ numerous steps(cascades): -Often involve the use of second messengers to facilitate the cascade -Amplify a signal response in a cell -Provide different points at which the response can be regulated Small water soluble, non-protein molecules or ions that pass on a signal (Live in the cytoplasmwater) Spread rapidly by diffusion Activate relay proteins Examples -camp -Ca2+ -Inositol Trisphosphate (IP3) camp Activates a number of protein kinase
Calcium Ions More widely used the camp Used as a secondary messenger in both G- protein pathways and tyrosine-kinase receptor pathways Inositol Trisphosphate (IP3) Secondary messenger attached to phospholipid of the cell membrane Sent to Ca channels on the ER Allows a flood of Ca2+ into the cytoplasm from the ER, activating a cell response Cellular Response Cytoplasmic regulation Regulation of gene expression -Transcription regulation in the nucleus (DNA- >RNA) Cytoplasmic Regulation Rearrangement of the cytoskeleton Opening or closing of an ion channels Alteration of cell metabolism
Transcription Regulation Activating protein synthesis for new enzymes Transcription control factors are often activated by a protein kinase If liver and heart cells both are exposed to ligands, why does one respond and the other not? Different cells have different collections of receptors Apoptosis (Programmed cell death) An elaborate ex of cell signaling that causes controlled cell suicide During this process the cell is dismantled and digested through many CS pathways to protect neighboring cells from damage Triggered by signals that activate a cascade of suicide proteins in cells In vertebrates, this is a normal part of development for our nervous immune systems