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Wednesday, January 8 th :. QUESTION TO PONDER: How do cells of the body communicate? . Cell Communication Chapter 11. Via cellular phones. Why do cells communicate?. If they didn’t, you would cease to exist. Regulation - cells need to control cellular processes.
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Wednesday, January 8th: QUESTION TO PONDER: How do cells of the body communicate? Cell Communication Chapter 11 Via cellular phones
Why do cells communicate? If they didn’t, you would cease to exist • Regulation - cells need to control cellular processes. • Environmental Stimuli - cells need to be able to respond to signals from their environment.
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 Contact • Through signal molecules
Direct Contact • When molecules can flow directly from cell to cell without crossing membranes. • Plants - plasmodesmata • Animals - gap junctions 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. • Double reason why they can’t cross cell membranes. • 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. • Mechanisms: 1. G-Protein linked 2. Tyrosine-Kinase 3. Ion channels 4. Intracellular
Fight-or-flight response • What is meant by the term “fight-or-flight”? Fight or Flight Response A Real Example of Cell Communication
G-protein linked • Plasma membrane receptor. • Works with “G-protein”, an intracellular protein with GDP or GTP. • What is GTP? • Guanosinetriphosphate: works to form ATP • GTP is also essential to signal transduction in living cells, where it is converted to GDP through GTPases. • GTP is readilty converted to ATP.
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. • Many diseases work by affecting g-protein linked receptors. • Ex - whooping cough, botulism, cholera, some cancers Nearly 60% of medications exert their effects this way
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 ofTyrosine-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. • LIGAND-GATED ION CHANNELS • 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. • Ex - steroids (hormones), NO - nitric oxide 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 (phosphate) from ATP to a protein. • About 1% of our genes are for Protein Kinases.
Protein Phosphorylation • The addition of Pi (phosphate) 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. • 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 G-protein 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.
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
Apoptosis • Balance between signals for “live” or “die” • Triggered by mitochondria damage, neighbor cells, internal signals • Involved with Parkinson’s Alzheimer’s, Cancer