Albinism Research Today is a free monthly online journal that collates and summarizes the latest research about Albinism, including details on pigmentation, genetic trait, heritability.

Involvement of OA1, an Intracellular GPCR, and G{alpha}i3, its Binding Protein, in Melanosomal Biogenesis and Optic Pathway Formation.

Young A, Powelson EB, Whitney IE, Raven MA, Nusinowitz S, Jiang M, Birnbaumer L, Reese BE, Farber DB

Jules Stein Eye Institute and the Molecular Biology Institute, UCLA, UCLA School of Medicine, Los Angeles, California, United States.

PURPOSE. Ocular albinism type 1 (OA1) is characterized by abnormalities in retinal pigment epithelium (RPE) melanosomes and misrouting of optic axons. The OA1 gene encodes a G-protein-coupled receptor (GPCR) that co-immunoprecipitates with the Galphai-subunit of hetrotrimeric G-proteins from human melanocyte extracts. This study was undertaken to test if one of the Galphai proteins, Galphai3, signals in the same pathway as OA1 to regulate melanosome biogenesis and axonal growth through the optic chiasm. METHODS. Adult Galphai3-/- and Oa1-/- mice were compared with their respective control mice (129Sv and B6/NCrl) to study the effects of the loss of Galphai3 or Oa1 function. Light and electron microscopy were used to analyze the morphology of the retina and the size and density of RPE melanosomes, electroretinograms (ERGs) to study retinal function, and retrograde labeling to investigate the size of the uncrossed optic pathway. RESULTS. While Galphai3-/- and Oa1-/- photoreceptors were comparable to those of the corresponding control retinas, the density of their RPE melanosomes was significantly lower than in control RPEs. Many of these melanosomes were ~2.3 and 3.8 larger than the largest 129Sv and B6/NCrl melanosomes, respectively. Although Galphai3-/- and Oa1-/- mice had normal ERGs, retrograde labeling showed a significant reduction from control in the size of their ipsilateral retinofugal projections. CONCLUSIONS. Our results indicate that Galphai3, like Oa1, plays an important role in melanosome biogenesis. Furthermore, they suggest a common Oa1-Galphai3 signaling pathway that ultimately affects axonal growth through the optic chiasm.

Published 1 April 2008 in Invest Ophthalmol Vis Sci.
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