Lecture 12 Flashcards
ion channel coupled receptors
receptors change the mb potential, transducer a chemical signal to an electrical signal
imp in nerve cells and electrically excitable cells (muscle cells)
signal binds to channel, diff configuration, opens, changes mb potential of cell, AP is triggered
G protein coupled receptors
activate mb bound trimeric GTP binding proteins
activate mb bound trimeric G proteins
trimeric = 3 subunits
all G protein cupled recepts have similar structures
largest family of cell surface receptors, and 800 types in humans
involved in physiological processes, small, taste, light detection, neurotrasnmition and immune responses.
a singel polypeptide chain that crosses the lipid bilayer 7x.
trimeric G protein
subunits, what each part does
activation process
is a mb protein, att to lipids in mb to alpha nad gamma subunits
3 subentries, alpha, beta, gamma,
alpha = binds and hydrolyzes GTP
beta = peripheral = int w alpha nad gamma
inactive = binds GDP
signal binds to receptor and receptor changes conformation, G protein also changes cone , now loses affinity to GDP, binds to GTP
now is activated, loses affinity for beta and gamma, alpha gets separated.
now has 2 new intracell singaling molecules that can activate others and transmit the signal
the trimeric g protein is a molecular switch
the alpha subunit switches itelf off by hydrolyzing the GTP to GDP.
G protein regulating ion channels
ex. pacemaker cells in heart = det heart rate
acetylcholine = slows heart rate.
Ach binds to receptors, changes cone, activates G protein,
the activated, beta/gamma complex int w the closed K channels, changes its conformation and opens. K follows conc grad, flows out, mb potential hyper polarized = harder for AP to occur, rate of contraction dec = heart slows.
G proteins activating mb bound enzymes.
most common enzymes = adenylyl cyclase (converts ATP to cAMP) and phospholipase C (breaks phospholipids in mb= produces IP3 and DAG)
DAG, IP3, and cAMP are 2nd messengers.
cAMP signalling pathway, PKA
signaling molecule activates GPCR, activates alpha subunit which actives adenylyl cyclase. so ATP =>cAMP.
cAMP activates PKA
PKA then can phosphorylate many diff proteins to activate them
ex. in muscle cells, PKA activates phosphorylase kinase.
can also turn on genes
cAMP pathway termination
for pathway to be stopped, cAMP must be destroyed, by cAMP phosphodiesterase.
phosphatidylinositol signal pathway
signal binds to GPCR, activates it, activates G protein, activates phospholipase C,
phospholipase C cleaves PIP2, into IP3 and DAG,
IP3 diffuses through cytoplasm, binds to IP3 receptors on ER, changes conf of receptor, open pathway, CA leaves lumen to cytoplasm,
DAG stays in cytoplasm and activates PKC with help of released Ca
PKC = phosphorylates/activates proteins involved in cell proliferation and differentiation
Ca as an intracellular signaling molecules
phosphatidylinositol pathway causes rise in Ca in cell
CA binding changes the shape of Ca sensitive proteins, like CaM
CaM changes confirmed of target enzymes like Ca/CaM dependent protein kinase.
the inc in intracell. Ca conc can lead to exocytosis
there are vesicles filled with saliva or NTs
protein in mb of vesicles and plasma mb int w eachtoher but not enough to fuse for exocytosis
we need another protein, but w/o Ca, the protein won’t int with this mb-mb interaction
when protein is bound to Ca, changes conference and int, makes fusion happen and exocytosis occurs.
NO synthase in endothelial cells activated after Ca binding
Ach binds to GPCR, activates G protein, activated phospholipid C, PLC cleaves PIP2 Ito IP3, IP3 causes Ca release from ER,
ACh binds to M3 muscarinic receptors on endothelial cells (that’s the signal).
This activates a Gq protein, which then activates phospholipase C (PLC).
PLC cleaves PIP₂ into IP₃
causes Ca²⁺ release from the ER.
Ca activates NO synthase, makes NO from arginine
NO diffuses across mb to smooth muscles,
binds to a protein enzyme that makes GTP to cGMP = relaxes smooth muscles.
GPCR + cAMP signaling in odor perception
odorant binds to receptor, a GPCR on olfactory neurons in the nose
activates a G protein,
activates adenylyl cyclase, ATP to cAMP, opens ions that depolarize the cell, sending electrical signal = AP
signal is relayed in glomeruli
relayed to higher brain regions.
GPCR + phosphatidylinositol signaling in taste perception
taste molecules bind to receptors on taste buds
activates G protein
activates phospholipase C,
cleaves PIP2 to IP3
IP3 binds to receptors on ER and releases Ca,
DAG = activated a Ca sensitive ion channel
leads to cell depolarization + release of NTs = send taste signal to brain
GPCR in light detection
no light = CGMP is continuously made
cGMP binds to cation channels, keeps open
w light = GPCR + G protein = activated
G protein activates cGMP phosphodiesterase = breaks down cGMP to GMP
no cGMP = Na channels close = cell hyperpolaization = less NTs (glutamate) being released = light detected = begins the process of seeing
light signal amplifiers in rod cells
each GPCR activates hundreds of G proteins
each G protein activates many cGMP phosphodiesterase enzymes
each deactivates hundred of cGMP
closes huge number of Na channels
