KIAA0702
NCKX1
SLC24A1
UniProt:O60721 SLC24A1
DHRS3
UniProt:O75911 DHRS3
LRAT
UniProt:O95237 LRAT
LDLR
UniProt:P01130 LDLR
RBP3
UniProt:P10745 RBP3
ABCA4
ABCR
UniProt:P78363 ABCA4
GRK1
RHOK
UniProt:Q15835 GRK1
RPE65
UniProt:Q16518 RPE65
C7orf18
NAPEPLD
UniProt:Q6IQ20 NAPEPLD
PLB
PLB1
UniProt:Q6P1J6 PLB1
ARSDR1
CGI-82
PSDR1
RDH11
UniProt:Q8TC12 RDH11
RDH1
RDH5
UniProt:Q92781 RDH5
RDH12
UniProt:Q96NR8 RDH12
PRRDH
RDH8
UniProt:Q9NYR8 RDH8
ABCA4 mediates atRAL transport
atRAL(membrane) is transported to atRAL(cytosol) by ABCA4
Defective STRA6 does not transport atROL
Defective LRAT does not esterify atROL and PALM to RPALM
Defective ABCA4 does not transport atRAL or NRPE from disc membranes
Defective OPN1SW causes tritanopia
Defective OPN1MW causes DCB and BCM
Defective OPN1MW causes COD5
Defective OPN1LW causes BCM
Defective OPN1LW causes CBP
Defective RDH12 does not reduce atRAL to atROL and causes LCA13
Defective RDH12 does not reduce atRAL to atROL and causes RP53
Defective RDH5 does not oxidise 11cROL to 11cRAL and causes RPA
Defective RBP4 does not bind atROL
atRAL can spontaneously react with PE to form NRPE
NRPE condenses with atRAL to form A2PE
A2PE hydrolyses to A2E
A2E is phagocytosed
A2E translocates to RPE cells
Digestion of retinyl palmitate by extracellular PTL:colipase
PNLIP:CLPS hydrolyses RPALM to atROL and PALM
Cleavage of retinyl palmitate by PLB1
PLB1 hydrolyses RPALM to atROL
Membrane retinol binds to cytosolic RBP2
atROL binds to RBP2
BCMO1:Fe2+ oxidises betaC to atRAL
Oxidation of beta-carotene to all-trans-retinal
atRAL binds to RBP2
RDH11 reduces RBP2:atRAL to RBP2:atROL
AKRs reduce RBP2:atRAL to RBP2:atROL
LRAT esterifies RBP2:atROL and FACYLs to atREs
atREs binds to nascent CM
Chylomicron secretion into the lymphatic system
Cytosolic CMs translocate to extracellular region
Nascent CMs transform into mature CMs
LPL hydrolyses TGs from mature CMs
Lipoprotein lipase (LPL) hydrolyses triacylglycerols (TGs) from mature chylomicrons (CM)
Circulating chylomicron remnants can be directly cleared by the LDL receptor
LDLR transports extracellular CR:atREs to cytosol
CR remnants bind to apoE, enhanced by HSPG, in preparation for internalisation
CR:atREs binds apoE and HSPG
LRPs transport extracellular CR:atREs:HSPG:apoE to cytosol
Remnant CMs bound to apoE and HSPG are cleared by LDL receptor-related proteins
NREH hydrolyses atREs to atROL and FAs
Retinyl esters are hydrolysed to retinol in hepatocytes
NREH hydrolyses atREs (HSPG:apoE) to atROL and FAs
Retinyl esters (complexed with HSPG:apoE) are hydrolysed to retinol in hepatocytes
atROL binds RBP1 (parenchymal cell)
Parenchymal atROL translocates to HSCs
atROL delivered to stellate cells for storage
atROL binds RBP1
LRAT esterifies RBP1:atROL and FACYLs to atREs
A REH hydrolses atREs to atROL and FAs
HSC cytosolic atROL translocates to extracellular region
atROL secreted into bloodstream
RBP4 binds atROL
RBP4:atROL binds TTR
TTR:RBP:atROL binds to STRA6 receptor
All-trans-retinol is taken up by cells expressing STRA6 receptor
atROL (extracellular) is transported to cytosol by STRA6
Before esterification, retinol binds to RBP1 in RPE
atROL binds RBP1 to form RBP1:atROL
LRAT esterifies all-trans-retinol in RPE
RPE65 isomero-hydrolyses atREs to 11cROL
Retinoid isomerohydrolase isomero-hydrolyses retinyl esters to 11-cis-retinol
RDHs oxidise 11-cis-retinol to 11-cis-retinal
RDHs oxidise 11cROL to 11cRAL
RDH5 oxidises 11-cis-retinol to 11-cis-retinal
RDH5 oxidises 11cROL to 11cRAL
11cRAL (RPE) translocates to photoreceptor outer segment
11-cis-retinal binds to rhodopsin
11cRAL binds to opsin to form RHO:11cRAL
Photons induce isomerization of 11cRAL to atRAL
Rhodopsin activation
NRPE is a substrate for ABCA4
NRPE dissociates to atRAL and PE
atRAL diffuses through membranes to cytosol
atRAL(membrane) diffuses to atRAL(cytosol)
RDH12 reduces atRAL to atROL
RDH8 reduces atRAL to atROL
RBP3 regulates the transport of atROL from ROS to RPE
RBP3 regulates atROL taken up by Muller cells
An atROL isomerase isomerises atROL to 11cROL
A REH hydrolyses 11cRE to 11cROL
11cROL translocates from Muller cells to cone photoreceptor cells
11cROL binds to RLBP1 to form RLBP1:11cROL
RLBP1 binds atROL
11cRDH oxidises 11cROL to 11cRAL
Photons induce isomerisation of 11cRAL to atRAL
atRAL is hydrolysed from R*
atRAL is reduced to atROL
MII catalyses GDP/GTP exchange on Gt
Gt-GTP dissociates to GNAT1-GTP and GNB1:GNGT1
GNAT1-GTP binds PDE6 and activates it
PDE hydrolyses cGMP to GMP
cGMP:CNG transports Na+ and Ca2+ into the rod outer segment
NCKX1 exchanges Na+ for Ca2+/K+
NCKX1 removes Ca2+ from the rod outer segment
Decreased cGMP closes cation channels
cGMP dissociates from CNG channels
METAP1/2 demethylates GNAT1
NMT1/2 transfer MYS to GNAT1
FNTA:FNTB transfers FARN to GNGT1
Farnesyltransferase complex farnesylates the gamma subunit of transducin
Unknown N-acyltransferase N-acylates glycine residue in GNAT1
Unknown NAT N-acylates Gly in GNAT1
GRK1 phosphorylates MII to p-MII
GRK1 phosphorylates MII to p-S334,S338,S343-MII
Ca2+ and recoverin restrict GRK1 activity
RCVRN:Ca2+ binds to and inhibits GRK1
SAG binds p-MII to form p-MII:SAG
atRAL dissociates from p-MII:SAG
p-MII:SAG dissociates to p-RHO and SAG
PP2A dephosphorylates p-RHO to RHO
GNAT1-GTP hydrolyses its bound GTP to GDP
PRKCA/Q phosphorylate RGS9-1:GN5B:RGS9BP
PRKCA/Q phosphorylate RGS9-1:GN5B:RGS9BP to form p-S478-RGS9-1:GN5B:RGS9BP
GNAT1-GDP binds to GNB1:GNGT1
GUCA binds Ca2+ to form GUCA:Ca2+
GUCYs converts GTP to cGMP
cGMP synthesis by guanylyl cyclase
cGMP binds CNG channel to form cGMP:CNG channel
CALM1:Ca2+ binds CNG channel
Calmodulin:Ca2+ lowers CNG channel sensitivity to cGMP
Diseases associated with visual transduction
Retinoid cycle disease events
Biosynthesis of A2E, implicated in retinal degradation
Visual phototransduction
Retinoid metabolism and transport
The canonical retinoid cycle in rods (twilight vision)
The retinoid cycle in cones (daylight vision)
The phototransduction cascade
Activation of the phototransduction cascade
Inactivation, recovery and regulation of the phototransduction cascade