Lecture 8 Flashcards

1
Q

3 small molecule signaling mechanisms

A
  1. independant of plasma membrane proteins
  2. ion channels
  3. downstream of G-protein-coupled receptors
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2
Q

can small hydrophobic molecules freely diffuse across the membrane? where do they usually bind in the cell?

A

yes
nuclear receptor superfamily proteins

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3
Q

nuclear receptor superfamily protein structure

A

N-terminal transcription activating domain
middle: DNA binding domain
C-terminal: ligand binding domain
both the receptor and effector

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4
Q

are all nuclear receptor proteins localized to nucleus

A

no, some stay in cytoplasm until binding to signal molecule then move to nucleus

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5
Q

does nitric oxide interact with the nuclear receptor superfamilies

A

no, acts in smooth muscle cells of blood vessels to relax them
can only dissuse short distance

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6
Q

is light a ligand

A

no but it’s a signal

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7
Q

synaptic signaling uses what type of receptor

A

extracellular ligand gated ion channels, ligand binding opens channel

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8
Q

GPCR structure

A

7 TM domains and extracelular signal receptor that becomes active upon binding to act as GEF: exchanges GDP for GTP in G protein

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9
Q

G protein structure

A

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!

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10
Q

how to turn off GPCR-G protein signaling

A

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

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11
Q

are there different kinds of G proteins

A

yes! also don’t all rely on just alpha

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12
Q

how is cAMP made and turned off

A

adenylyl cyclase makes cAMP using ATP
phosphodiester enzymes break down cAMP to AMP to turn signaling pathway off

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13
Q

does cAMP activate or inactivate PKA? how?

A

activate
inactive PKA has 4 subunits: 2 regulatory and 2 catalytic (kinases)
2 cAMP bind to 2 regulatory subunits, releasing kinases so active

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14
Q

where does PKA go?

A

nucleus to phosphorylate CREB protein ACTIVATING it to promote transcription of certain genes
also activates other proteins

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15
Q

CRE

A

cAMP-responsive element

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16
Q

olfactory neuron

A

express just 1 type of GPCR but different neurons will express different GPCRs

17
Q

what happens when an odorant is recognized by a GPCR

A

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

18
Q

does the brain interpret single or combined activation of olfactory neurons

A

combined activation of multiple neurons that brain interprets as certain smell

19
Q

phospholipase C-beta

A

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

20
Q

does opening the ion channel through phospholipase C-beta lead to calcium entry or release from ER?

A

high Ca concentration in ER lumen so calcium is released into cytoplasm

21
Q

what is the final result of phospholipase C-beta signalling?

A

calcium and diacylglycerol bind and activate protein kinase C

22
Q

protein kinase C

A

phosphorylates downstream proteins
acts like a coincidence detector - needs both diacyl glycerol and calcium to be active

23
Q

Golf

A

G protein in olfactory neurons

24
Q

Gq

A

DAG, IP3, Ca2+ and PKC

25
Q

how is PKC like a coincidence detector

A

needs both calcium ions from IP3 ion channel activation at the ER to release calcium and diacylglycerol from the initial cleavage of PIP