Chapter 11 Cell Communication Question? • How do cells communicate? – By “cellular” phones. ;) • But seriously, cells do need to communicate for many reasons. Why do cells communicate? • Regulation - cells need to control cellular processes. • Environmental Stimuli - cells need to be able to respond to signals from their environment. Cell Communication Cell Signaling (C.S.) • Is a relatively “new” topic in Biology and AP Biology. • Appears to answer many questions in medicine. • Is a topic you’ll be hearing more about in your future. Stages of C.S. 1. Reception - receiving the signal. 2. Transduction - passing on the signal. 3. Response - cellular changes because of the signal. Reception Transduction Response Reception • The target cell’s detection of a signal coming from outside the cell. • May occur by: – Direct Contact – Through signal molecules Direct Contact • When molecules can flow directly from cell to cell without crossing membranes. • Plants - plasmodesmata • Animals - gap junctions Direct Contact • May also occur by cell surface molecules that project from the surface and “touch” another cell. Signal Molecules • The actual chemical signal that travels from cell to cell. • Often water soluble. • Usually too large to travel through membranes. – 2 reasons why they can’t cross cell membranes. Signal Molecules • Behave as “ligands”: a smaller molecule that binds to a larger one. Receptor Molecules • Usually made of protein. • Change shape when bind to a signal molecule. • Transmits information from the exterior to the interior of a cell. Receptor Mechanisms 1. G-Protein linked 2. Tyrosine-Kinase 3. Ion channels 4. Intracellular G-protein linked • Plasma membrane receptor. • Works with “G-protein”, an intracellular protein with GDP or GTP. G-protein • GDP and GTP acts as a switch. • If GDP - inactive • If GTP - active G-protein • When active (GTP), the protein binds to another protein (enzyme) and alters its activation. • Active state is only temporary. G-protein linked receptors • Very widespread and diverse in functions. • Ex - vision, smell, blood vessel development. G-protein linked receptors • Many diseases work by affecting g-protein linked receptors. • Ex - whooping cough, botulism, cholera, some cancers G-protein linked receptors • Up to 60% of all medicines exert their effects 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 substrate protein. 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. Intracellular Proteins • Become activated & cause the cellular response. Tyrosine-Kinase Receptors • Often activate several different pathways at once, helping regulate complicated functions such as cell division. 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+. Ion-channel Receptors • 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. • Ex - steroids (hormones), NO - nitric oxide Intracellular Signals • Activated protein turns on genes in nucleus. Comment • 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. • Often has multiple steps using relay proteins such as Protein Kinases. Protein Kinase • General name for any enzyme that transfers Pi from ATP to a protein. • About 1% of our genes are for Protein Kinases. Protein Phosphorylation • The addition of Pi to a protein, which activates the protein. • Usually adds Pi to Serine or Threonine. Amplification • Protein Kinases often work in a cascade with each being able to activate several molecules. • Result - from one signal, many molecules can be activated. Secondary Messengers • Small water soluble non-protein molecules or ions that pass on a signal. • Spread rapidly by diffusion. • Activates relay proteins. Secondary Messengers • Examples - cAMP, Ca2+, inositol trisphosphate (IP3) cAMP • A form of AMP made directly from ATP by Adenylyl cyclase. • Short lived - converted back to AMP. • Activates a number of Protein Kinases. Calcium Ions • More widely used than cAMP. • Used as a secondary messenger in both Gprotein pathways and tyrosine-kinase receptor pathways. Calcium Ions • Works because of differences in concentration between extracellular and intracellular environments. (10,000X) • Used in plants, muscles and other places. Inositol Trisphosphate (IP3) • Secondary messenger attached to phospholipids of cell membrane. • Sent to Ca channel on the ER. • Allows flood of Ca2+ into the cytoplasm from the ER. Start here Or Start here Cellular Responses • Cytoplasmic Regulation • Transcription Regulation in the nucleus (DNA -> RNA). Cytoplasmic Regulation • Rearrangement of the cytoskeleton. • Opening or closing of an ion channel. • Alteration of cell metabolism. Transcription Regulation • Activating protein synthesis for new enzymes. • Transcription control factors are often activated by a Protein Kinase. Question • 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. Alternate explanation Comment • Chapter focused only on activating signals. There are also inactivation mechanisms to stop signals. Signaling Efficiency • Often increased by the use of scaffolding proteins. • Scaffolding proteins – a protein that holds or groups signal pathway proteins together. Apoptosis • • • • Programmed cell death Uses cell signaling pathways DNA is chopped up Cell shrinks and becomes lobed (blebbing) • Pieces are digested by specialized scavenger cells WBC before and after Apoptosis • Balance between signals for “live” or “die” • Triggered by mitochondria damage, neighbor cells, internal signals • Involved with Parkinson’s, Alzheimer’s, Cancer Summary • Don’t get bogged down in details in this chapter. Use the KISS principle. • Know - 3 stages of cell signaling. • Know - At least one example of a receptor and how it works (in detail). Summary • Know - protein kinases and cascades (amplification) • Know – example of a secondary signal • Apoptosis