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 distance Figure 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 space receptor: EnvZ Figure 15.2 transduction: >autophosphorylate EnvZ >phosphorylate OmpR, >activate OmpC amplification: one gene, many proteins effect: 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 receptor Figure 15.4

Receptors different types of receptors react to signals differently –gated ion channels regulate passage of Na +, K + Ca 2+, 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 receptor is a protein kinase Figure 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 activation Figure 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 steps Figure 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 (IP 3 ) and diacylglycerol (DAG) DAG activates a membrane-bound, Ca 2+ -dependent protein kinase C (PKC) IP 3 opens a Ca 2+ channel in ER membrane Ca 2+ activates PKC PKC phosphorylates many cellular target molecules

phosphatidyl inositol bisphosphate phospholipase C IP 3 + DAG glycerol phosphate DAG IP 3

second messengers IP 3 & DAG activate PKC Figure 15.11

Transducers second messengers can trigger multiple responses one signal –Ca 2+ is a common second messenger a steep Ca 2+ gradient exists across ER & plasma membranes opening gated Ca 2+ channels raises cytoplasmic [Ca 2+ ] Ca 2+ activates many cellular targets Ca 2+ activation often involves calmodulin

Transducers second messengers can trigger multiple responses one signal –nitric oxide (NO) is a gas –NO synthase is activated by Ca 2+ in response to IP 3 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 –Ca 2+ channels open very briefly & Ca 2+ pumps remove Ca 2+ 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 protein Figure 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 glycogen stores in the liver Figure 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 communication Figure ~ 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 plasmodesmata Figure 15.17