Lecture 8 Flashcards
- independant of plasma membrane proteins
- ion channels
- downstream of G-protein-coupled receptors
can small hydrophobic molecules freely diffuse across the membrane? where do they usually bind in the cell?
yes
nuclear receptor superfamily proteins
nuclear receptor superfamily protein structure
N-terminal transcription activating domain
middle: DNA binding domain
C-terminal: ligand binding domain
both the receptor and effector
are all nuclear receptor proteins localized to nucleus
no, some stay in cytoplasm until binding to signal molecule then move to nucleus
does nitric oxide interact with the nuclear receptor superfamilies
no, acts in smooth muscle cells of blood vessels to relax them
can only dissuse short distance
is light a ligand
no but it’s a signal
synaptic signaling uses what type of receptor
extracellular ligand gated ion channels, ligand binding opens channel
GPCR structure
7 TM domains and extracelular signal receptor that becomes active upon binding to act as GEF: exchanges GDP for GTP in G protein
G protein structure
heterotrimeric large G-protein complex: alpha, beta and gamma
alpha subunit has GDP, exchanged for GTP by active GPCR
active GTP bound G-alpha dissociates from beta and gamma
when beta and gamma separate from alpha, they also become an active dimer!
how to turn off GPCR-G protein signaling
G-alpha is actually a GTPase so over time will hydrolyze GTP to GDP
regulator of G protein signaling (RGS): very slow on it’s own though so GAP protein increases rate of GTP hydrolysis to GDP
are there different kinds of G proteins
yes! also don’t all rely on just alpha
how is cAMP made and turned off
adenylyl cyclase makes cAMP using ATP
phosphodiester enzymes break down cAMP to AMP to turn signaling pathway off
does cAMP activate or inactivate PKA? how?
activate
inactive PKA has 4 subunits: 2 regulatory and 2 catalytic (kinases)
2 cAMP bind to 2 regulatory subunits, releasing kinases so active
where does PKA go?
nucleus to phosphorylate CREB protein ACTIVATING it to promote transcription of certain genes
also activates other proteins
CRE
cAMP-responsive element
olfactory neuron
express just 1 type of GPCR but different neurons will express different GPCRs
what happens when an odorant is recognized by a GPCR
olfactory neuron specific G protein complex called Golf triggering cAMP production
odorant activates receptor
receptor activates G protein
G alpha activates adenylyl cyclase
instead of activating PKA, cAMP opens intracellular cAMP gated/ion channels
ions flow into cell triggering action potential in olfactory neuron
does the brain interpret single or combined activation of olfactory neurons
combined activation of multiple neurons that brain interprets as certain smell
phospholipase C-beta
alternate downstream activation for GPCR-G protein
cleaves phospholipids - specifically PIP
cleaves in 2 into diacylglycerol (DAG) lipid that stays in the membrane
and IP3 - sugar head group with phosphates - small soluble molecule that can open ligand gated ion channels (specifically Calcium in ER)
both DAG and IP3 are small molecule signals
does opening the ion channel through phospholipase C-beta lead to calcium entry or release from ER?
high Ca concentration in ER lumen so calcium is released into cytoplasm
what is the final result of phospholipase C-beta signalling?
calcium and diacylglycerol bind and activate protein kinase C
protein kinase C
phosphorylates downstream proteins
acts like a coincidence detector - needs both diacyl glycerol and calcium to be active
Golf
G protein in olfactory neurons
Gq
DAG, IP3, Ca2+ and PKC
how is PKC like a coincidence detector
needs both calcium ions from IP3 ion channel activation at the ER to release calcium and diacylglycerol from the initial cleavage of PIP
