Wednesday, January 8 th :

Wednesday, January 8th:

Cell CommunicationChapter 11

QUESTION TO PONDER:How do cells of the body communicate?

Via cellular phones

If they didn’t, you would cease to exist

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.

Stages of cell signaling1. 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 linked2. Tyrosine-Kinase3. Ion channels4. Intracellular

What is meant by the term “fight-or-flight”?

Fight or Flight ResponseA Real Example of Cell Communication

Fight-or-flight response

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 thisway

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.

Mechanism1. 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)

cAMPA 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.

ApoptosisProgrammed cell deathUses cell signaling pathwaysDNA is chopped upCell shrinks and becomes lobed (blebbing)

Pieces are digested by specialized scavenger cells

WBC before and after

ApoptosisBalance 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