Cell Signaling&

Communication

Cellular Signaling•cells respond to various types of signals

•signals provide information about a cell’s environment

signal molecules are

chemically

diverse

gaseous hydrocarbon

steroid

catecholamine

peptide

Signal Receptors•cells respond to signals only if they have the right signal receptors–receptors bind or absorb specific signals

–cells without appropriate receptors “ignore” specific signals

some signals communicate local information

some signals communicate over long distanceFigure 15.1

•signaling evokes specific responses from specific cells–a signal does not specify a cell’s response

–a cell’s response is determined by the cell

Cell Responses

•The “Fight or Flight” Response–epinephrine (adrenaline) is released into the blood stream

–receptors in different tissues bind epinephrine•heart: beats faster, more strongly•digestive system: blood vessels constrict•liver: cleave glycogen; release glucose•adipose tissue: breaks down triglycerides

Cell Responses

•cell responses involve three components–receptor–transduction mechanism (amplifier)

–effect

Cell Responses

change in the environment

signal: solute in intermembrane spacereceptor: EnvZFigure 15.2

transduction: >autophosphorylate EnvZ >phosphorylate OmpR, >activate OmpC amplification: one gene, many proteinseffect: block pores

Receptors •each cell makes a specific group of receptors so it can respond to a specific set of signals–many in the plasma membrane –some in the cytoplasm or the nucleoplasm

•a receptor has a binding site for its ligand, the signal molecule

•ligand binding causes a conformational change in the receptor

Human growth hormone

Human growth Hormone receptor

Figure 15.3

ligand binding causes a

conformational change in the

receptorFigure 15.4

Receptors

•different types of receptors react to signals differently–gated ion channels•regulate passage of Na+, K+ Ca2+, Cl-

•ligand binding causes the channel to open

acetylcholine receptor responds to acetylcholine

Figure 15.5

Receptors•different classes of receptors react to signals differently–receptor protein kinases•ligand binding activates a cytoplasmic kinase domain–dimerizaton often occurs–autophosphorylation further activates the receptor–phosphorylation of cellular targets begins signal transduction

insulin recepto

r is a

protein kinaseFigure 15.6

Receptors•different classes of receptors react to signals differently–G protein-linked receptors•ligand binding causes the receptor to bind an inactive G protein-GDP•G protein is activated to G protein-GTP•GTP-bearing subunit diffuses to effector•effector initiates cell response–G protein may activate or inhibit effector

signal binding & G-protein activationFigure 15.7

Receptors•different classes of receptors react to signals differently–cytoplasmic receptors bind nonpolar ligands•ligand binding lets the receptor enter the nucleus & activate transcription

–nuclear receptors bind ligands in the nucleus•receptors without bound ligands repress transcription•ligand binding activates transcription

Figure 15.8

Transducers

•signal transduction–converting the information “signal X has arrived” into a cellular response

–may be “direct” by the activated receptor

–may be “indirect” by a second messenger

–enzymatic steps in signal transduction pathways amplify signal strength

transduction of a growth

factor signal

amplifies the signal at

several stepsFigure 15.9

Transducers •second messengers can trigger multiple responses one signal–cAMP•synthesized by a G protein-activated membrane-bound adenylyl cyclase•binds to ion channels in some cells•binds to protein kinases in other cells•may do both in some cells

cAMP synthesis

from ATP

Figure 15.10

Transducers •second messengers can trigger multiple responses one signal–receptor activates G protein activates effector, phospholipase C

–phospholipase C cleaves PTI into inositol triphosphate (IP3) and diacylglycerol (DAG)•DAG activates a membrane-bound, Ca2+-dependent protein kinase C (PKC)•IP3 opens a Ca2+ channel in ER membrane•Ca2+ activates PKC•PKC phosphorylates many cellular target molecules

phosphatidyl inositol bisphosphat

e

phospholipase C

IP3 + DAG

glycerol

phosphate

DAG

IP3

second messengers IP3 & DAG activate PKCFigure 15.11

Transducers•second messengers can trigger multiple responses one signal–Ca2+ is a common second messenger•a steep Ca2+ gradient exists across ER & plasma membranes•opening gated Ca2+ channels raises cytoplasmic [Ca2+]•Ca2+ activates many cellular targets•Ca2+ activation often involves calmodulin

Transducers•second messengers can trigger multiple responses one signal–nitric oxide (NO) is a gas–NO synthase is activated by Ca2+ in response to IP3 after an acetylcholine receptor binds its ligand

–NO diffuses to a neighboring smooth muscle cell and activates an enzyme causing relaxation

smooth muscle relaxation response to acetylcholine

signa

Relax!!

Figure 15.13

Regulation of Signal Transduction

•activation of signal transduction is opposed by inactivating factors–NO breaks down very rapidly–Ca2+ channels open very briefly & Ca2+ pumps remove Ca2+ immediately

–protein phophatases inactivate P-enzymes

–GTPases return G proteins to inactive form

–cAMP is converted to AMP•members of different types of pathways interact in regulatory roles

Effects •cell responses include –opening membrane channels•important in sensory cells –odorant receptors send nerve impulses to the brain

activated G protein activates adenylyl cyclase

cAMP opens ion channels to signal the brain

1. odorant receptors are displayed on the surface of nasal epithelial cells;

2. each receptor binds a particular odorant molecule;

3. odorant binding activates a G proteinFigure 15.14

Effects •cell responses include –opening of membrane channels–alteration of enzyme activities•covalent modification (phosphorylation) or allosteric modification (cAMP) cause expose active sites–glycogen metabolism in the liver is regulated by a protein kinase cascade in response to epinephrine

epinephrine

causes glucose release from

glycogenstores in the liverFigure 15.15

Effects

•cell responses include –opening of membrane channels–alteration of enzyme activities

–changes in gene transcription•a common response is new protein synthesis–the Ras pathway stimulates cell division in response to growth factors

a signal to divide & its transduction pathway

Figure 15.9

Direct Intercellular Communication

•animal cells communicate directly, through gap junctions–small molecules diffuse between cells•ATP•second messengers•waste or nutrient molecules

–tissue function can be coordinated

gap junctions between

adjacent animal cells allow direct

communicationFigure 15.16

~ 1 nm

Direct Intercellular Communication

•plant cells communicate through plasmodesmata–lined by plasma membrane–occupied by desmotubules–permit rapid exchange of small molecules

plant cells communicate via plasmodesmataFigure 15.17