GPCR - sensory Flashcards

1
Q

sensory GPCRs responsibly for…?

main second messengers

A

olfactory perceptions

gustatory perceptions

visual perception

cyclic nts:
cAMP + cGMP

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2
Q

olfactory epithelium consists of

A

olfactory neurones

supporting cells

basal stem cells

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3
Q

where are olfactory receptors found?

A

on the cilia of olfactory neurones

-> expands the SA

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4
Q

perception of smell by olfactory neurones

- process

A
  1. odorant binds to Golf-alpha GPCR in PM of cilia
  2. activates alpha subunit of G protein
  3. activated adenylyl cyclase
  4. converts ATP->cAMP
    = increases [cAMP]
  5. NA+ channels open
  6. membrane depolarisation
  7. action potential
  8. signal relayed to target neurones in brain
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5
Q

genetic control over OR expression

A

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

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6
Q

which 3 classes of taste molecules are sensed by GPCRs?

- and potentially?

A

sweet
bitter
umami

fatty acids

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7
Q

when are sweet, umami and fatty acids perceived as pleasant or aversive?

A

pleasant at low-moderate conc

aversive at high conc

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8
Q

where do neurones perceive taste?

A

on modified cilia on the tongue

cluster of neurones
-> forms taste bud

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9
Q

knock out of mouse G-alpha gustducin

A

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

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10
Q

neuronal wiring

- explains odour + taste interpretation

A

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

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11
Q

importance of wiring

- mouse experiment

A

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

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12
Q

vertebrate eye

- features

A

photoreceptors in retina:

rod cells - light/dark
GPCR rhodopsin coupled to Gt-alpha transducin

cone cells - colour
GPCR photopsin

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13
Q

rod cell

- structure

A

outer segment
- rhodopsin receptors embedded in membrane discs

inner segment
- organells inc. mitochondria

cell body
- contains nucleus

synaptic region
- constitutive inhibitory neurotransmitter release

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14
Q

photoconversion of 11-cis-retinal to all-trans-retinal

A

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

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15
Q

light signal transduction

- at rest (dark)

A

cAMP-gated NA+ channels allow Na+ influx

keeps membrane depolarised

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16
Q

light signal transduction

- in light

A

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

17
Q

how does signal transduction lead to activation of post-synaptic neurones?

A

hyper polarised membrane

-> turns off release of inhibitory neurotransmitters e.g. glutamate

18
Q

signalling cascades important for?

what is necessary for returning to resting state?

A

signal amplification
-> increases sensitivity to signal
so can detect v low [signal]

regulation at all levels

19
Q

signal reversal 1

- raising cGMP levels

A
  1. [Ca2+] decrease
  2. activates recoverin
  3. stimulates guanylyl cyclase
  4. converts GTP -> cGMP
  5. cGMP reassociates with Na2+ channels to open them
  6. membrane depolarisation
20
Q

signal reversal 2

- RGS proteins stimulate GTP hydrolysis activity of a-transducin

A

1.inactivation of transducin
prevents further activation of cGMP phosphodiesterase

  1. [Ca2+] increase
  2. Na+ channels open
  3. membrane depolarisation
21
Q

signal reversal

- Ca2+ out via cGMP-gated Na+ channels

A

cGMP-gated Na+ channels permeable to Ca2+
-> [Ca2+] decrease in light

  • > low [Ca2+] stimulates guanylyl cyclase
  • > [cGMP] increases
22
Q

signalling adaptation in vision of different light levels

A

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