FATP1 inhibits 11-cis retinol formation via interaction with the visual cycle retinoid isomerase RPE65 and lecithin:retinol acyltransferase.
The isomerization of all-trans retinol (vitamin A) to 11-cis retinol in the retinal pigment epithelium (RPE) is a key step in the visual process for the regeneration of the visual pigment chromophore, 11-cis retinal. LRAT and RPE65 are recognized as the minimal isomerase catalytic components. However, regulators of this rate-limiting step are not fully identified and could account for the phenotypic variability associated with inherited retinal degeneration (RD) caused by mutations in the RPE65 gene. To identify new RPE65 partners, we screened a porcine RPE mRNA library using a yeast two-hybrid assay with full-length human RPE65. One identified clone (here named FATP1c), containing the cytosolic C-terminal sequence from the fatty acid transport protein 1 (FATP1 or SLC27A1, solute carrier family 27 member 1), was demonstrated to interact dose-dependently with the native RPE65 and with LRAT. Furthermore, these interacting proteins colocalize in the RPE. Cellular reconstitution of human interacting proteins shows that FATP1 markedly inhibits 11-cis retinol production by acting on the production of all-trans retinyl esters and the isomerase activity of RPE65. The identification of this new visual cycle inhibitory component in RPE may contribute to further understanding of retinal pathogenesis.
Guignard
Thomas J P
TJ
Inserm U583, Institut des Neurosciences de Montpellier, Montpellier 34091, France.
Jin
Minghao
M
Pequignot
Marie O
MO
Li
Songhua
S
Chassigneux
Yolaine
Y
Chekroud
Karim
K
Guillou
Laurent
L
Richard
Eric
E
Hamel
Christian P
CP
Brabet
Philippe
P
D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism*; D050612:Fatty Acid Transport Proteins / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007313:Insecta; D051379:Mice; D010641:Phenotype; D012160:Retina / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D020798:Two-Hybrid System Techniques; D014801:Vitamin A / Q000037:antagonists & inhibitors* / Q000737:chemistry; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D000217:Acyltransferases; D002352:Carrier Proteins; D005136:Eye Proteins; D050612:Fatty Acid Transport Proteins; D005982:Glutathione Transferase; D014801:Vitamin A; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C493568:SLC27A1 protein, human; C056942:lecithin-retinol acyltransferase