Ch. 11: Cell Communication

I. Introduction:A. Cell to cell communication is absolute essential for multicellular organisms.

-coordinate activitiesII. An Overview of Cell Signaling

A. Cell signaling evolved earlyB. Simple organisms like the yeast

Saccharomyces cerevisiae (bread, beer)identifies its mates by chemical signaling.

1. Two sexes: a and α(alpha).

2. They secrete a specific signaling molecule, “a factor” and “alpha factor” respectively.

3.These factors each bind to receptor proteins on the other mating type.

4. They move towardsone another and fuse,“mating,” which combines genes.

C. This is an example of a signal-transductionpathway: a signal on a cell’s surface causes changes inside the cell.

D. Signaling pathway probably evolved:Prokaryotes Single-celled eukaryotes Multicellular eukaryotes.

1. Prokaryote: Myxobacteria

-little food causes the colony to form a spore until food is abundant.

E. Communicating cells can be far apart or close together.

1. Short distance: Cells can release “localregulators” that influence cells near them.

a. Paracrine signaling: When numerouscells receive a signal simultaneously.

b. Synaptic signaling: nerve cells releaseneurotransmitters to a single target cell that is very close. An electricalimpulse signals the release of theneurotransmitters.

2. Long distance: hormones are released inboth plant and animal cells between cellsthat are far apart.

a. Animals: hormonesare released into the blood and will travelto target cells.(example: insulin)

b. Plants: hormones may travel in vessels, but more often travel from cell to cell or by diffusion in air.(example: ethylene)

3. Communication by direct contact: -Gap junctions in animal cells-Plasmodesmata in plant cells-_____________________ in cell to cell recognition Glycoproteins/glycolipids

F. The three stages of cell signaling:(Researched by Earl Sutherland, who won the Nobel Prize in 1971.)

1. Reception: Target cells receives signal.2. Transduction: Signal molecules changes

the receptor protein, initiating transduction pathway.

3. Response: The signal triggers a cellularresponse.

III. Signal Reception and the Initiation ofTransductionA. The signal molecule changes the receptor

protein shape.1. The signaling molecule is called a

“ligand,” which is a small molecule thatbinds to a larger molecule.

B. Signal receptors are membrane proteins.When they are activated, they can causecellular activities. C. There are 3 types of signal receptors:

1. G-protein-linked receptors: consists of a receptor protein associated with a G-protein on the cytoplasmic side.

a. The receptor is seven alpha helices spanning the membrane.

b. The G protein acts like an on-off switch: When a signal

binds to the binding protein, it causes the G protein to become activated.

-When the G protein is activated, GTP is bound and GDP is replaced.-The activated G protein then signals to a molecule that will cause a cellular response inside the cell.

-The G protein can also act as a GTPase enzyme and hydrolyzes the GTP to GDP. This will inactivate the signaling.

-G-protein systems are involved in many human diseases like cholera, whooping cough, and botulism. These infections interfere with G-protein function.2. The second type of signal receptors -

Tyrosine-Kinase Receptors: a. This type of receptor attaches

phosphates from ATP to substrate protein tyrosines.

b. Tyrosine-kinase receptors are oftenthe receptors for “growth factors.”

d. The fully-activated receptor proteins activate a variety of specific relay proteins that bind to specific phosphorylated tyrosine molecules.

e. One tyrosine-kinase receptor dimer may activate ten or more different intracellular proteins simultaneously.

c. When ligands bind to two receptors polypeptides, the polypeptides aggregate, forming a dimer.

3. The third type of signal receptor:Ligand-gated ion channels

a. When a ligand binds to the channelproteins, they open or close in response to a chemical signal.

b. This allows or blocks ion flow, such as Na+ or Ca2+.

c. When the liganddissociates fromthe protein, it willclose.

d. Ligand-gated ion channels are very important in the nervous system thatare controlled by electrical signals.

D. Not all receptors are membrane proteins:Intracellular Receptors1. Some signal receptors in the cytosol or

nuclear membrane. This requires the signals to be able to pass through themembrane.

a. Hydrophobic steroidsb. Hormonesc. Nitric oxide (NO)

Testosterone like other hormones, travels through the blood and enters cells throughout the body.In the cytosol, they bind and activate receptor proteins. The activatedproteins enter the nucleus where they willturn on genes that control male characteristics.

2. These activated proteins act as transcription factors. Transcription factors control which genes are turned on - that is, which genes are transcribed into messenger RNA (mRNA).

IV. Signal-Transduction PathwayA. The transduction stage of signaling is

usually a multistep pathway that amplifiesthe signal (exponential).B. Pathways relay signals from receptors to

cellular responses.1. In a signal pathway, the signal molecule

is not passed down. Relay molecules relay the signal along a pathway.

C. Protein phosphorylation is a major mechanism of signal transduction.

1. Relay proteins are phosphorylated byATP via protein kinases.

2. Most phosphorylation occurs at either serine or threonine amino acids of the substrate protein.

3. Many of the relay molecules in a signal-transduction pathway are protein kinases that lead to a “phosphorylation cascade”.

Inactive -> active

4. 1% of our genes code for protein kinases.5. Abnormal protein kinase activity can lead

to abnormal cell growth, which can cause cancer.

6. Protein phosphatases turn off signal transduction pathways by removing phosphates off from proteins.

D. Not all signal-transduction pathway molecules are proteins. Some are small molecules and ions that are involved in signaling pathways. They are called second messengers).

2. Two of the most important second messengers are cyclic AMP (cAMP) and Ca2+.

1. Second messengers participate in pathways initiated by both G-protein-linked receptors and tyrosine-kinase receptors.

a. A signal moleculeactivates a G protein that activates adenylyl cyclase in the plasma membrane.

b. Adenylyl cyclasetriggers the formation of cAMP,which will act as asecond messengerin the pathway.cAMP will activateprotein kinase.

c. cAMP converts to inactive AMP very rapidly (via phosphodiesterase). In order for a cell to produce more cAMP,it will need to receive a signal moleculeover again.

3. Certain bacteria can disrupt G proteinsignaling pathway.

a. Cholera is caused by a bacteria that colonizes the the small intestine and produces a toxin that modifies a G protein that regulates salt and water secretion.

b. The modified G protein is stuck in its active form, continuously stimulating productions of cAMP.

This causes a person to secrete large amounts of water and salts into the intestines, which will be excreted out as diarrhea.

4. Many signal molecules in animals can cause an increase in Ca2+ (calcium ions)in the cytosol of a cell.

a. Cells use Ca2+ as a second messenger in both the G-protein pathways andthe tyrosine-kinase pathways.

b. Cells normally have a higher concentration of Ca2+ outside of the cell.

c. Signal-transduction pathways trigger the release of Ca2+ from the cell’s ER.

d. Phospholipase C splits a special phospholipid in the membrane into IP3 and DAG. IP3 then stimulates therelease of Ca2+ into the cytosol.

V. Cellular Responses to SignalsA. In response to a signal, a cell may regulate

activities in the cytoplasm or transcription in the nucleus.

1. Ion channels may open up2. Stimulate metabolism (epinephrine

breaks down glycogen)

3. Some signaling pathways don’t activateenzymes, but the synthesis of enzymes

and proteins:

Stimulates the “transcription of a protein” by turning on a gene.

4. The same signal may produce differentresponses, depending on the cell receiving the signal:-epinephrine causes liver cells to break down glycogen.-epinephrine in cardiac cells causes them to contract.This could only mean that different cells have different signal receptors, relay proteins, and proteins that carry out the response.

5. Scaffolding proteins:

Can trigger multiple protein kinasesat once.

6. Defects in relay proteins can cause disease:The inherited disorder, Wiskott-Aldrich syndrome (WAS), is due to the absence of a single relay protein.It leads to abnormal bleeding, eczema, and a predisposition to infections and leukemia.