Intracellular signalling I

Question 1

2 types of signals

Answer 1

biotic (all living organisms)

abiotic (light/temperature/smell/sound/mechanical stress)

Question 2

intracellular signalling pathway

Answer 2

1) receiving
2) transduction
3) transforming
4) responding

Question 3

effector proteins

Answer 3

metabolic enzymes
ion channels
gene regulators
cytoskeletal proteins

Question 4

themes in intracellular signalling

Answer 4

-conformational changing of shape
-reversible post-translational modification
-2nd messengers amplify signal
-cytoplasm to nucleus motility
-feedback modulates response to signal

Question 5

ON/OFF switches signalling

Answer 5

signalling by phosphorylation: ON - protein kinase OFF - protein phosphatase
signalling by GTP-binding: ON-GEFs (guanine nucleotide exchange factor) OFF - GDP via GAPs (GTPase activating protein)

Question 6

positive feedback

Answer 6

extends duration of a cellular response to a signal

Question 7

negative feedback

Answer 7

delay (used in circadian rhythm)
generates oscillatory response to non-oscillatory signal

Question 8

receptor for plasma membrane signals

Answer 8

permeable signal molecules use intracellular receptors (hydrophobic signal molecule)
non-permeable signal molecule use cell-surface receptor (hydrophilic signal molecule)

Question 9

nuclear receptors

Answer 9

transcription factors
activated by hydrophobic signal molecules
steroid hormones: estradiol, cortisol, thyroxine

Question 10

nitric oxide (NO)

Answer 10

hydrophobic, small gas enters plasma membrane
NO synthesised from arginine in endothelial cells via NO synthase (NOS)

Question 11

NO signalling

Answer 11

NO bounds to guanylyl cyclase
GTP converted to cyclic GMP
cGMP activated protein kinase
rapid relaxation of smooth muscle cells

Question 12

4 receptor categories for hydrophilic signal molecules

Answer 12

ion channels coupled/ionotropic
receptors controlling the proteolysis of latent regulators (notch, wnt,hedgehog)
enzyme-coupled receptors
GPCRs

Question 13

GPCR structure

Answer 13

7 transmembrane helices
G protein complex contains: a.b.y
human genome encodes > 700 GPCRs

Question 14

GPCR binding

Answer 14

ligand binding
forms binding pocket
Ga converts GDP to GTP
Gby and Ga dissociate causing activation of effector protein which amplifies and transduces signals
Ga acts as a GTPase: GTP—>GDP
subunits join

Question 15

cAMP and pKA

Answer 15

long term changes in gene expression
cAMP synthesised from ATP via adenylate cyclase
pKA = cAMP effector
PKA contains 2 regulatory and 2 catalytic subunits

Question 16

cAMP signalling

Answer 16

NA binds to b-adrenergic receptors
Gs activated (stimulators G protein)
Gs-GTP activates AC
AC catalyses production of cAMP from ATP
cAMP activates pKA (4 cAMP onto 2 regulatory subunits)
Catalytic subunits of pKA releases
pKA is active
Translocates proteins from cytoplasm to nucleus
Activated CREB binds to CRE (cyclic AMP response element)
Transcription

Question 17

CNG

Answer 17

cAMP directly controls cyclic nucleotide gated channels (CNGs) in olfactory sensory neurons (OSNs)
CNG channels open causing depolarisation

Question 18

Rhodopsin (GPCR)

Answer 18

Activates PDE
DARK high density of cyclic GMP channels open - depolarisation
LIGHT- PDE cleaves cyclic GMP- closes CNG channels- hyperpolarised

Question 19

Which stimuli are regulated by PLC and PKC signalling

Answer 19

Bitter
Sweet
Umami

Question 20

PLC signalling

Answer 20

Metabotropic receptors become activated
Gq activated
Gq-GTP activates PLC
PLC catalyses conversion of PIP2 to DAG and IP3 (2nd messengers)
DAG binds to and activates PKC (requires increased calcium levels)
Ca2+ binds to CaM
CaM activates CaMKII

Question 21

Taste bud receptor signalling

Answer 21

By dimer activates PLC
PIP2 converted to DAG and IP3
Ca2+ and ATP released
ATP binds to P2X receptors in sensory neurons
Action potential

Question 22

CaMKII regulation

Answer 22

Positive feedback