Intracellular signalling I Flashcards
2 types of signals
biotic (all living organisms)
abiotic (light/temperature/smell/sound/mechanical stress)
intracellular signalling pathway
1) receiving
2) transduction
3) transforming
4) responding
effector proteins
metabolic enzymes
ion channels
gene regulators
cytoskeletal proteins
themes in intracellular signalling
-conformational changing of shape
-reversible post-translational modification
-2nd messengers amplify signal
-cytoplasm to nucleus motility
-feedback modulates response to signal
ON/OFF switches signalling
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)
positive feedback
extends duration of a cellular response to a signal
negative feedback
delay (used in circadian rhythm)
generates oscillatory response to non-oscillatory signal
receptor for plasma membrane signals
permeable signal molecules use intracellular receptors (hydrophobic signal molecule)
non-permeable signal molecule use cell-surface receptor (hydrophilic signal molecule)
nuclear receptors
transcription factors
activated by hydrophobic signal molecules
steroid hormones: estradiol, cortisol, thyroxine
nitric oxide (NO)
hydrophobic, small gas enters plasma membrane
NO synthesised from arginine in endothelial cells via NO synthase (NOS)
NO signalling
NO bounds to guanylyl cyclase
GTP converted to cyclic GMP
cGMP activated protein kinase
rapid relaxation of smooth muscle cells
4 receptor categories for hydrophilic signal molecules
ion channels coupled/ionotropic
receptors controlling the proteolysis of latent regulators (notch, wnt,hedgehog)
enzyme-coupled receptors
GPCRs
GPCR structure
7 transmembrane helices
G protein complex contains: a.b.y
human genome encodes > 700 GPCRs
GPCR binding
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
cAMP and pKA
long term changes in gene expression
cAMP synthesised from ATP via adenylate cyclase
pKA = cAMP effector
PKA contains 2 regulatory and 2 catalytic subunits
cAMP signalling
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
CNG
cAMP directly controls cyclic nucleotide gated channels (CNGs) in olfactory sensory neurons (OSNs)
CNG channels open causing depolarisation
Rhodopsin (GPCR)
Activates PDE
DARK high density of cyclic GMP channels open - depolarisation
LIGHT- PDE cleaves cyclic GMP- closes CNG channels- hyperpolarised
Which stimuli are regulated by PLC and PKC signalling
Bitter
Sweet
Umami
PLC signalling
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
Taste bud receptor signalling
By dimer activates PLC
PIP2 converted to DAG and IP3
Ca2+ and ATP released
ATP binds to P2X receptors in sensory neurons
Action potential
CaMKII regulation
Positive feedback
