Ocular Albinism Type 1 - Localization of The OA1 Protein

Localization of The OA1 Protein

Shen, et al. created fusion proteins between OA1 and GFP. Melanosomal localization of OA1 has been confirmed by immuno-electron microscopy and other techniques alike. Localization patterns of wild type OA1-GFP and mutated OA1-GFP were compared. The wild type OA1 localized to late endosomal or lysosomal compartments. This is supported by data from Samaraweera, et al. that OA1 colocalizes with Lamp1, which is a marker for late endosomal compartment. Hence, OA1 might traffick itself out of this compartment to the melanosomes.

In addition to retina and melanoma, OA1 protein product was also detected in human pigment cells like melanosomal membrane glycoprotein. This suggests that OA1 might be involved in melanosome biogenesis. Coimmunoprecipitation studies of OA1 with G_β and G_αi in melanocyte extracts revealed its specific interaction with G_αi. Moreover, since OA1 is an organellar GPCR, it may represent an unidentified pathway in the melanosome. Until recently, it was believed that the probable ligand for OA1 might be within the melanosomal lumen, maybe one of the components of the melanogenic pathway since it is so closely related to melanosome biogenesis. This has been proved now.

Studies by Samaraweera, et al. revealed OA1 as an endolysosomal protein. Schiaffino, et al. already proved that it is an integral membrane protein. Newton et al. have shown that it has three probable glycosylation sites. Furthermore, OA1 was found to be stimulated by α-melanocortin stimulating hormone but inhibited by agouti signal protein. The fact that OA1 responds to melanin modifiers indicates its probable role in melanogenesis. Just like other melanosomal proteins TYR and TRP-1, processing of OA1 also occurs in the golgi. Endogenous OA1 protein expressed by normal human melanocytes is detected as a 60kDa protein.