Cell Communication Chapter 11 Wednesday, January 8th: Cell Communication Chapter 11 QUESTION TO PONDER: How do cells of the body communicate? 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? Guanosine triphosphate: 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 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. 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.

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. At least one example of a receptor and how it works (in detail). protein kinases and cascades (amplification) example of a secondary signal Apoptosis