Flashcards in Exam 2 Koh- Retina Biochem 1 Deck (69):
How is vision started?
Photon absorption by the visual pigments in cone and rods
Retinal circuit integrates ____ analog info of photoreceptors into a digital signal at the ______ cell level
What are the 2 laminar structures of the retina?
Outer retinal pigment epithelium (RPE) and inner neural retina
What is the origination of the laminar structures?
Laminar structures arise from an invagination of the embryonic optic cup that folds an ectodermal layer into apex-to-apex contact with itself
How thick are photoreceptors?
~200 micrometers thick
The photoreceptors transduce light into an _______ signal
Amacrine cells are ______ interneurons
How many amacrine cells are there?
How many morphological types of ganglion cells are there?
Mammals other than primates have what types of cones?
Only 2 types (L and S cones)
What is the function of photoreceptors?
Detect food source, mate, predator/prey, orientation
What are opsins?
Visual pigments, a vitamin A-based chromophore, a seven-transmembrane-helix apoprotein, prototypical G protein-coupled receptors
How are signals transduced?
Signal via heterotrimeric G proteins
How many opsins are in the animal kingdom?
What are opsins structurally similar to?
Bacteriorhodopsin and channelopsins
What are the 2 major groups of opsins?
R and C
Rhabdomeric photoreceptors _______ to light
What motif does r-opsin use for phototransduction?
Ciliary vertebrate rods and cones _________ to light
What motif does c-opsin use for phototransduction?
Rod phototransduction is good for understanding other sensory transduction in _____ and _____
Olfaction and taste
Where does rod phototransduction take place?
In the cell's ciliary outer segment
How many rhodopsins?
1 billion rhodopsins per ROS
Retinitis pigmentosa is caused by mutations in the gene for ______
What leads to autosomal dominant retinitis pigmentosa?
Improperly folded or constitutively activated protein
What leads to autosomal recessive retinitis pigmentosa?
Impaired activation or reduced opsin level
Supplementation with natural or synthetic retinoids may slow photoreceptor degeneration owing to _____ _____
What happens to mice with a knockout mutation in the rod opsin gene?
Fail to form rod OS and have no rod electroretinographic (ERG) response, but show a cone response early in life
When do cone photoreceptors disappear?
3 months of age
What light does rhodopsin absorb best?
Green, insensitive to red light
Rod rhodopsins are _______ and cone reodopsins are ______
What does rod rhodopsin consist of?
A combination of opsin (apoprotein), 11-cis-retinal (prosthetic group), and Lys 296
What does cone rhodopsin consist of?
In cone outer segments with opsin-like apoproteins and 11-cis-retinal
Upon photon absorption, 11-cis-retinal isomerizes to ________
Metarhodopsin II activates _____, the G protein of phototransduction
How is dark current maintained?
By cGMP-gated cation channels at night
How does the dark current depolarize the cell?
To ~30 mV to sustain synaptic-transmitter (glutamate) release, neural signals for vision
In rods, what is the proportion of Rh:Gt: PDE?
One activated rhodopsin activates how many transducins?
20 transducins activate how many PDE molecules?
Each PDE hydrolyzes cyclic GMP at what?
How many cyclic GMP hydrolyzed per activated rhodopsin? How many sodium channels are closed?
10^4, several hundred sodium channels are closed
What happens when rods are deactivated in the dark?
For complete deactivation, each active component must shut down, Rh* (corresponding to the meta-II state of Rh, decays over a minute into an inactive state (meta-III). Long before this decay Rh* is phosphorylated by a rhodopsin kinase (G protein-coupled- receptor- kinase 1)
What is rhodopsin desensitisation?
Followed rapidly by the binding of another protein, arrestin (Arr), which recognizes phosphorylated Rh* (Rh*-P). Rh*-P still has perhaps some activity, but the Rh*~P-Arr loses all activity
How many phosphorylation sites are on rhodopsin?
6-7 C terminal phosphorylation sites, many need to be phosphorylated for the normal decay of the response
What happens in dephosphorylation and reactivation?
Regenerated rhodopsin loses its bound arrestin and is dephosphorylated by phosphatase 2A
How long is the slowest step of transducin?
~200 ms in mouse
What is CNG?
A tetrameric complex composed of A and B subunits, each with a single cGMP-binding site
CNG is ______ to monovalent and divalent cations
What is the affinity for cGMP?
With free cGMP at ~1 micrometer in darkness, only ~1% of the channels, or ~10^4 out of an overall 10^6 channels are open
Why are only 1% open of cGMP channels?
Providing a fast response to light
How much does Ca2+ carry?
~15% of the dark inward current, the rest being carried largely by Na+
In darkness, steady Ca2+ influx is balanced by an equal Ca2+ efflux via a ________
Na/Ca, K exchanger
In the light, the closure of cGMP-gated channels stops the Ca2+ influx, but the Ca2+ efflux continues, thus _____ the intracellular free Ca2+
Calcium decrease leads to what 3 things?
GC activity increase, GC activity requires 2 quanylate cyclase activating proteins, GCAP1 and GCAP2 which are Ca2+- binding proteins that are negatively modulated by Ca2+ binding
What happens to guanylate cyclase with high calcium in the dark?
~600 nM keeps GC in check, in the light, the Ca2+ decrease disinhibits the GCAPs, thus activating GC, producing negative feedback
What is GRK1 modulated by?
Negatively modulated by Ca2+ through another Ca2+ binding protein: recoverin or S-modulin so that Rh* phosphorylation (arrestin binding) is moderately slow in dim light
What happens to Ca2+ in brighter light?
Accelerates when Ca2+ progressively decreases in brighter light, reducing the active lifetime of Rh*
Calcium decrease leads to _____ in affinity of CNG channels to cGMP
Calcium decrease leads to what 2 things?
High Ca2+ reduces the affinity of cGMP for the channel, so some channels initially closed by light reopen as Ca2+ falls
Cone phototransduction is less _____ but faster in ______
Does cone or rod phototransduction have faster adaptation?
What is the difference between rod phototransduction and cone phototransduction?
Gt is less efficiently activated by Rh*, the effective lifetime of cone R* is also much shorter, GRK7 has a much higher specific activity and more abundant than GRK1, GTPase activity of Gtalpha- GTP and hence its deactivation are more rapid in cones, Ca2+ feedback is also faster in cones
What proteins are located in the sac?
Rhodopsin, transducin, PDE, rhodopsin kinase, arrestin, recoverin, guanylate cyclase, dehydrogenase
What proteins are located in the rim of the sac?
Peripherin, ROM-1, ABC transporter
What proteins are located in the membrane?
cGMP gated channel, glucose transporter, Na/K, Ca exchanger
What proteins are located in the sac and cytoplasm?
Ca-dependent GCAP and calmodulin
What protein is located in the inner segment?