The Ocular Albinism Type 1 Gene Product is a Membrane Glycoprotein Localized to Melanosomes

Ocular albinism type 1 (OA1) is an inherited disorder characterized by severe reduction of visual acuity, photophobia, and retinal hypopigmentation. Ultrastructural examination of skin melanocytes and of the retinal pigment epithelium reveals the presence of macromelanosomes, suggesting a defect in...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-08, Vol.93 (17), p.9055-9060
Main Authors: Schiaffino, M. Vittoria, Baschirotto, Cinzia, Pellegrini, Graziella, Montalti, Simona, Tacchetti, Carlo, De Luca, Michele, Ballabio, Andrea
Format: Article
Language:English
Subjects:
Albinism, Ocular - metabolism
Cell Compartmentation
Cell lines
COS cells
Cryoultramicrotomy
Detergents
Epithelial cells
Eye Proteins - genetics
Eye Proteins - immunology
Eye Proteins - isolation & purification
HeLa cells
Humans
Melanocytes
Melanocytes - chemistry
Melanocytes - ultrastructure
Melanoma
Melanosomes
Membrane Glycoproteins - genetics
Membrane Glycoproteins - immunology
Membrane Glycoproteins - isolation & purification
Membrane proteins
Microscopy, Immunoelectron
Pigment Epithelium of Eye - chemistry
Protein Processing, Post-Translational
Recombinant Proteins
Retinal pigments
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Summary:Ocular albinism type 1 (OA1) is an inherited disorder characterized by severe reduction of visual acuity, photophobia, and retinal hypopigmentation. Ultrastructural examination of skin melanocytes and of the retinal pigment epithelium reveals the presence of macromelanosomes, suggesting a defect in melanosome biogenesis. The gene responsible for OA1 is exclusively expressed in pigment cells and encodes a predicted protein of 404 aa displaying several putative transmembrane domains and sharing no similarities with previously identified molecules. Using polyclonal antibodies we have identified the endogenous OA1 protein in retinal pigment epithelial cells, in normal human melanocytes and in various melanoma cell lines. Two forms of the OA1 protein were identified by Western analysis, a 60-kDa glycoprotein and a doublet of 48 and 45 kDa probably corresponding to unglycosylated precursor polypeptides. Upon subcellular fractionation and phase separation with the nonionic detergent Triton X-114, the OA1 protein segregated into the melanosome-rich fraction and behaved as an authentic integral membrane protein. Immunofluorescence and immunogold analyses on normal human melanocytes confirmed the melanosomal membrane localization of the endogenous OA1 protein, consistent with its possible involvement in melanosome biogenesis. The identification of a novel melanosomal membrane protein involved in a human disease will provide insights into the mechanisms that control the cell-specific pathways of subcellular morphogenesis.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.17.9055