Cell responses to environment-- Signals

Cell responses to environment-- Signals

Signal transduction can coordinate: Development Formation of tissues Timing of cell division Direction of cell enlargement Size and shape of organs Responses to environment Food (and other chemicals) Light Gravity...

Structure of the human ß2- adrenergic receptor (red) embedded in a lipid membrane and bound to a diffusible ligand (green), with cholesterol (yellow) between the two receptor molecules. A cartoon of the lipidic cubic phase used for crystalization of the receptor is shown in the background. (Control of enzyme activity and gene expression often involves receptors in the plasma membrane.)

Polar and charged compounds have p.m. receptors Hydrophobic signals can have cytoplasmic receptors Sodium Insulin (a protein) Acetylcholine Pressure Estrogen Cortisol Light

Transduction : the events beween stimulus and response Some signals involved in transduction steps: Phosphorylation (kinases, phosphatases) Voltage across a membrane Protein association/dissociation GTP, GTP hydrolysis (G proteins) Lipid metabolites (IP3: inositol triphosphate; DAG, diacylglycerol) Ca 2+ (cytoplasmic concentration), calmodulin camp, cgmp NO

Kinases are important in eukaryotic signaling Signal: insulin Receptor: in plasma membrane Transduction: change in receptor; kinase activation; phosphorylation of target

Signal transduction can involve ion transport across a membrane Opening of the acetylcholine receptor/sodium channel allows Na + to enter a muscle cell Flow of sodium changes the electric field across the membrane (less neg. inside) Voltage change opens adjacent Na + channels-- amplification--and Ca 2+ channels Ca 2+ stimulates actin-myosin association and contraction

Signal transduction can involve the release of an effector protein Signal: cortisol Receptor: bound to chaperone Transduction: change in receptor shape; release of receptor; transcription initiation

Biologists often speak of a signal cascade. What does cascade mean? (a) Waterfall (b) Shower of sparks (c) Mountain range in Washington state (d) Series of events related by causation

In signal transduction, one signal often leads to another ( cascade ) Signal: growth factor Receptor: kinase Transduction Ras (G protein); Raf, MEK, MAPk (kinases); transcription Note GTP hydrolysis at Ras

In signal transduction, one signal often leads to another Receptor G protein P-lipase C Ca 2+ channel Protein kinase C Note the lipid metabolites and Ca 2+

Cyclic AMP is a common second messenger

Cyclic AMP is involved in the release of glucose in the liver (camp starts a cascade of kinases)

Cyclic AMP is involved in the release of glucose in the liver (Last kinase activates phosphorylase enzyme directly, not enzyme synthesis)

Cyclic AMP is involved in odor perception Odorant/ receptor activates G protein G protein activates adenylyl cyclase camp opens ion channels (voltage impulse)

NO is an example of a diffusable (long-distance) signal G protein NO synthase cgmp voltage IP 3 Ca 2+

Summary: the types of signals are diverse Phosphorylation (kinases, phosphatases) Voltage across a membrane Protein association/dissociation GTP, GTP hydrolysis (G proteins) Lipid metabolites (IP3: inositol triphosphate; DAG, diacylglycerol) Ca 2+ (cytoplasmic concentration), calmodulin camp, cgmp NO

Summary: the effects of signals are diverse Transcription: new mrnas and proteins Activation of enzymes Opening of ion channels How can a few types of signals coordinate so many processes? Combinations: some signals work on multiple targets Combinations: some targets need multiple signals Differentiation: signals trigger functions in prepared cells

Neves, Science 296:1136, 2002

A recent article in Science identifies similar signal cascades in taste cells and respiratory tissues. Can you identify the signals? Kinnamon and Reynolds, Science 325:1081, 2009