GPCR - sensory Flashcards
sensory GPCRs responsibly for…?
main second messengers
olfactory perceptions
gustatory perceptions
visual perception
cyclic nts:
cAMP + cGMP
olfactory epithelium consists of
olfactory neurones
supporting cells
basal stem cells
where are olfactory receptors found?
on the cilia of olfactory neurones
-> expands the SA
perception of smell by olfactory neurones
- process
- odorant binds to Golf-alpha GPCR in PM of cilia
- activates alpha subunit of G protein
- activated adenylyl cyclase
- converts ATP->cAMP
= increases [cAMP] - NA+ channels open
- membrane depolarisation
- action potential
- signal relayed to target neurones in brain
genetic control over OR expression
each olfactory neurone expresses 1 receptor gene
1 / 2 alleles is randomly silenced
each cluster controlled by 1 enhancer element
-> interacts randomly with 1 receptor gene of the cluster
which 3 classes of taste molecules are sensed by GPCRs?
- and potentially?
sweet
bitter
umami
fatty acids
when are sweet, umami and fatty acids perceived as pleasant or aversive?
pleasant at low-moderate conc
aversive at high conc
where do neurones perceive taste?
on modified cilia on the tongue
cluster of neurones
-> forms taste bud
knock out of mouse G-alpha gustducin
alters discrimination of bitter + sweet tastes
WT = averse to salty, sour + bitter
preference for sweet
KO = fail to recognise biter substances until high conc
+ poor at recognising sweet substances
neuronal wiring
- explains odour + taste interpretation
recognition of 1000s of odourant molecules involves converting signal into common intracellular response via 2nd messengers
signal relayed to brain
connectivity between sensory cells + target cells processing the signal in the brain is important for recognising the signal
importance of wiring
- mouse experiment
transgenic mice
- with human-specific receptors
KO of specific receptors
-> loss of perception of specific substances
mice expressed bitter substance receptors in sweet-sensing neurones
-> resulted in mice liking the bitter taste
vertebrate eye
- features
photoreceptors in retina:
rod cells - light/dark
GPCR rhodopsin coupled to Gt-alpha transducin
cone cells - colour
GPCR photopsin
rod cell
- structure
outer segment
- rhodopsin receptors embedded in membrane discs
inner segment
- organells inc. mitochondria
cell body
- contains nucleus
synaptic region
- constitutive inhibitory neurotransmitter release
photoconversion of 11-cis-retinal to all-trans-retinal
retinal covalently attached to a lysine on the receptor
absorption of photon
-> converts from 11-cis-retinal to all-trans-retinal is relayed via conformational change of receptor
allows receptor to interact with G protein
light signal transduction
- at rest (dark)
cAMP-gated NA+ channels allow Na+ influx
keeps membrane depolarised
light signal transduction
- in light
light activates rhodopsin (GPCR)
- > activates transducin (g-protein)
- > stimulates cGMP phosphodiesterase (converts cGMP -> 5’-GMP)
-> [cGMP] decreases
- > cGMP leaves Na+ channels on PM
- > channels close
= membrane hyperpolarisation
how does signal transduction lead to activation of post-synaptic neurones?
hyper polarised membrane
-> turns off release of inhibitory neurotransmitters e.g. glutamate
signalling cascades important for?
what is necessary for returning to resting state?
signal amplification
-> increases sensitivity to signal
so can detect v low [signal]
regulation at all levels
signal reversal 1
- raising cGMP levels
- [Ca2+] decrease
- activates recoverin
- stimulates guanylyl cyclase
- converts GTP -> cGMP
- cGMP reassociates with Na2+ channels to open them
- membrane depolarisation
signal reversal 2
- RGS proteins stimulate GTP hydrolysis activity of a-transducin
1.inactivation of transducin
prevents further activation of cGMP phosphodiesterase
- [Ca2+] increase
- Na+ channels open
- membrane depolarisation
signal reversal
- Ca2+ out via cGMP-gated Na+ channels
cGMP-gated Na+ channels permeable to Ca2+
-> [Ca2+] decrease in light
- > low [Ca2+] stimulates guanylyl cyclase
- > [cGMP] increases
signalling adaptation in vision of different light levels
activated rhodopsin receptor recognised by rhodopsin kinase
RK phosphorylates serine/threonine residues on cytoplasmic portion of rhodopsin
-> reduces ability to activate transducin
Rhodopsin bound by arresting
-> becomes fully inactivated
