Chapter 5 Cell Signaling

You must know The three stages of cell signaling. The function of G protein-coupled receptors, ligand gated ion channels and intracellular receptors.

Review

The Three Stages of Cell Signaling Cells receiving signals undergo three processes Reception Transduction Response © 2014 Pearson Education, Inc. 4

Reception Plasma membrane protein EXTRACELLULAR FLUID CYTOPLASM Receptor The ligand is specific to the receptor Plasma membrane protein The binding between a signal molecule (ligand) and receptor is highly specific. Ligand binding generally causes a shape change in the receptor. Many receptors are directly activated by this shape change. Most signal receptors are plasma membrane proteins. Signaling Molecule A.K.A. ligand © 2014 Pearson Education, Inc. 5

Transduction EXTRACELLULAR FLUID CYTOPLASM Plasma membrane Reception Figure 5.20-2 EXTRACELLULAR FLUID CYTOPLASM Plasma membrane Reception Transduction Receptor Relay molecules Transduction is a step or series of steps that converts the signal to a form that can bind about a specific cellular response. Transduction usually requires a sequence of changes in a series of different molecules - a signal transduction pathway. Signaling molecule © 2014 Pearson Education, Inc. 6

Response The response may be almost any imaginable cellular activity… EXTRACELLULAR FLUID CYTOPLASM Plasma membrane Reception Transduction Response Receptor Activation Relay molecules The response may be almost any imaginable cellular activity – such as catalysis by an enzyme, rearrangement of the cytoskeleton, or activation of specific genes in the nucleus. Signaling molecule The response may be almost any imaginable cellular activity… © 2014 Pearson Education, Inc. 7

Reception Transduction Response

Receptors in the Plasma Membrane There are two main types of membrane receptors G protein-coupled receptors Ligand-gated ion channels Most water-soluble signal molecules bind to specific sites on receptor proteins that span the plasma membrane. The signal molecules do not enter the cell. Plasma membrane Receptor CYTOPLASM Plasma membrane protein Reception hydro philic signaling molecule 9

Importance of G protein-coupled receptors Nearly 1,000 different types that we know of. Nearly 60% of all medicines influence G protein-coupled receptors. Involved in: Embryonic development Senses of smell Sense of taste Maintaining homeostasis! Ex. Cholera, whooping cough, and botulism are caused by toxins that interfere with G protein-coupled receptors.

Signal (ligand) Receptor G protein in “off” conformation 1. The G protein is “off” because it is bound to GDP. (GDP is similar to ADP)

2. The ligand binds to the receptor. Signal (ligand) Receptor G protein in “off” conformation 2. The ligand binds to the receptor.

Signal (ligand) Receptor G protein in “off” conformation 3. The ligand binding to the receptor cause the receptor to change shape.

Signal (ligand) 4. The receptor changing shape is a switch that activates its G protein. The G protein releases the GDP molecule that kept it in an inactive state and binds to GTP instead.

Signal (ligand) Receptor G protein in “off” conformation 5. When GTP is attached, the G protein becomes activated and splits into two parts.

Signal (ligand) Receptor Second Messengers G protein in “off” conformation Cellular response Activated enzyme Second Messengers 6. One part of the “split” G protein activates a nearby enzyme that is embedded in the plasma membrane. The activated enzyme catalyzes the production of second messengers. The second messengers are small signaling molecules that diffuse rapidly to spread the signal throughout the cell and elicit a cellular response.

ligand-gated ion channel Ions diffuse through the open channel 1 Cellular response Gate open 2 Gate closed Ions Signaling molecule (ligand) Plasma membrane Ligand-gated ion channel receptor Gate closed 3 A ligand-gated ion channel receptor acts as a “gate” for ions when the receptor changes shape. When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor. Ligand-gated ion channels are very important in the nervous system. The diffusion of ions through open channels may trigger an electric signal. © 2014 Pearson Education, Inc. 17

Only cells that contain receptors for the signal can respond to it. Plasma membrane Hormone- receptor complex Receptor protein Hormone (testosterone) EXTRA- CELLULAR FLUID Hydrophobic DNA Plasma membrane Hormone- receptor complex Receptor protein New Hormone (testosterone) mRNA EXTRA- CELLULAR FLUID CYTOPLASM NUCLEUS Hydrophobic Plasma membrane Hormone (testosterone) EXTRA- CELLULAR FLUID Intracellular receptors Hydrophobic Only cells that contain receptors for the signal can respond to it. Intracellular receptor proteins are found in the cytosol or nucleus of target cells. Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors. Examples of hydrophobic messengers are the steroid and thyroid hormones of animals and nitric oxide (NO) in both plants and animals. Testosterone behaves similarly to other steroid hormones. Only cells that contain receptors for testosterone can respond to it. The hormone binds the receptor protein and activates it. The active form of the receptor enters the nucleus, acts as a transcription factor, and activates genes needed for male sex characteristics. Steroid hormone interacting with an intracellular receptor. 18