The ocular albinism type 1 (OA1) protein and the evidence for an intracellular signal transduction system involved in melanosome biogenesis.

Abstract

Ocular albinism type 1 is an X-linked disorder characterized by severe reduction of visual acuity, retinal hypopigmentation, foveal hypoplasia, optic misrouting and the presence of giant melanosomes (macromelanosomes) in skin melanocytes and retinal pigment epithelium. The protein product of the OA1 gene is a pigment cell specific membrane glycoprotein, displaying structural and functional features of G protein-coupled receptors (GPCRs). However, in contrast to all other previously characterized GPCRs, OA1 is not localized to the plasma membrane, but is targeted to intracellular organelles, namely late endosomes/lysosomes and melanosomes. These unique characteristics suggest that OA1 represents the first example described so far of an exclusively intracellular GPCR and regulates melanosome biogenesis by transducing signals from the organelle lumen to the cytosol. These findings support previous hypotheses that GPCR-mediated signaling might also operate at the internal membranes in mammalian cells.

• Authors: M Vittoria Schiaffino, Carlo Tacchetti
• Journal: Pigment cell research (Pigment Cell Res) Vol. 18 Issue 4 Pg. 227-33 (Aug 2005) ISSN: 0893-5785 [Print] Denmark
• PMID: 16029416 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Eye Proteins
• GPR143 protein, human
• Membrane Glycoproteins
• Receptors, G-Protein-Coupled

Topics

• Albinism, Ocular (metabolism)
• Amino Acid Sequence
• Animals
• Eye Proteins (genetics, metabolism)
• Humans
• Melanosomes (metabolism)
• Membrane Glycoproteins (genetics, metabolism)
• Molecular Sequence Data
• Mutation
• Pigment Epithelium of Eye (metabolism)
• Receptors, G-Protein-Coupled (genetics, metabolism)
• Sequence Homology, Amino Acid
• Signal Transduction