Chapter 11 Cell Communication

Question? u How do cells communicate? u By “cellular” phones. u But seriously, cells do need to communicate for many reasons.

Why do cells communicate? u Regulation - cells need to control cellular processes. u Environmental Stimuli - cells need to be able to respond to signals from their environment.

Cell Communication

Cell Signaling (C.S.) u Is a relatively “new” topic in Biology and AP Biology. u Appears to answer many questions in medicine. u 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 u The target cell’s detection of a signal coming from outside the cell. u May occur by: u u Direct Contact u u Through signal molecules

Direct Contact u When molecules can flow directly from cell to cell without crossing membranes. u Plants - plasmodesmata u Animals - gap junctions

Direct Contact u May also occur by cell surface molecules that project from the surface and “touch” another cell.

Signal Molecules u The actual chemical signal that travels from cell to cell. u Often water soluble. u Usually too large to travel through membranes. u Double reason why they can’t cross cell membranes.

Signal Molecules u Behave as “ligands”: a smaller molecule that binds to a larger one.

Receptor Molecules u Usually made of protein. u Change shape when bind to a signal molecule. u 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 u Plasma membrane receptor. u Works with “G-protein”, an intracellular protein with GDP or GTP.

G-protein u GDP and GTP acts as a switch. u If GDP - inactive u If GTP - active

G-protein u When active (GTP), the protein binds to another protein (enzyme) and alters its activation. u Active state is only temporary.

G-protein linked receptors u Very widespread and diverse in functions. u Ex - vision, smell, blood vessel development.

G-protein linked receptors u Many diseases work by affecting g-protein linked receptors. u Ex - whooping cough, botulism, cholera, some cancers

G-protein linked receptors u Up to 60% of all medicines exert their effects through G-protein linked receptors.

Tyrosine-Kinase Receptors u Extends through the cell membrane. u 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 u Become activated & cause the cellular response.

Tyrosine-Kinase Receptors u Often activate several different pathways at once, helping regulate complicated functions such as cell division.

Ion-channel Receptors u Protein pores in the membrane that open or close in response to chemical signals. u Allow or block the flow of ions such as Na + or Ca 2+.

Ion-channel Receptors u Activated by a ligand on the extracellular side. u Causes a change in ion concentration inside the cell. u Ex - nervous system signals.

Intracellular Signals u Proteins located in the cytoplasm or nucleus that receive a signal that CAN pass through the cell membrane. u Ex - steroids (hormones), NO - nitric oxide

Intracellular Signals u Activated protein turns on genes in nucleus.

Comment u Most signals never enter a cell. The signal is received at the membrane and passed on. u Exception - intracellular receptors

Signal-Transduction Pathways u The further amplification and movement of a signal in the cytoplasm. u Often has multiple steps using relay proteins such as Protein Kinases.

Protein Kinase u General name for any enzyme that transfers Pi from ATP to a protein. u About 1% of our genes are for Protein Kinases.

Protein Phosphorylation u The addition of Pi to a protein, which activates the protein. u Usually adds Pi to Serine or Threonine.

Amplification u Protein Kinases often work in a cascade with each being able to activate several molecules. u Result - from one signal, many molecules can be activated.

Secondary Messengers u Small water soluble non-protein molecules or ions that pass on a signal. u Spread rapidly by diffusion. u Activates relay proteins.

Secondary Messengers u Examples - cAMP, Ca 2+, inositol trisphosphate (IP 3 )

cAMP u A form of AMP made directly from ATP by Adenylyl cyclase. u Short lived - converted back to AMP. u Activates a number of Protein Kinases.

Calcium Ions u More widely used than cAMP. u Used as a secondary messenger in both G-protein pathways and tyrosine- kinase receptor pathways.

Calcium Ions u Works because of differences in concentration between extracellular and intracellular environments. (10,000X) u Used in plants, muscles and other places.

Inositol Trisphosphate (IP 3 ) u Secondary messenger attached to phospholipids of cell membrane. u Sent to Ca channel on the ER. u Allows flood of Ca 2+ into the cytoplasm from the ER.

Start here Or Start here

Cellular Responses u Cytoplasmic Regulation u Transcription Regulation in the nucleus (DNA --> RNA).

Cytoplasmic Regulation u Rearrangement of the cytoskeleton. u Opening or closing of an ion channel. u Alteration of cell metabolism.

Transcription Regulation u Activating protein synthesis for new enzymes. u Transcription control factors are often activated by a Protein Kinase.

Question u If liver and heart cells both are exposed to ligands, why does one respond and the other not? u Different cells have different collections of receptors.

Alternate explanation

Comment u Chapter focused only on activating signals. There are also inactivation mechanisms to stop signals.

Signaling Efficiency u Often increased by the use of scaffolding proteins. u Scaffolding proteins – a protein that holds or groups signal pathway proteins together.

Apoptosis u Programmed cell death u Uses cell signaling pathways u DNA is chopped up u Cell shrinks and becomes lobed (blebbing) u Pieces are digested by specialized scavenger cells

WBC before and after

Apoptosis u Balance between signals for “live” or “die” u Triggered by mitochondria damage, neighbor cells, internal signals u Involved with Parkinson’s Alzheimer’s, Cancer

Summary u Don’t get bogged down in details in this chapter. Use the KISS principle. u Know - 3 stages of cell signaling. u Know - At least one example of a receptor and how it works (in detail).

Summary u Know - protein kinases and cascades (amplification) u Know – example of a secondary signal u Apoptosis