title: Ocular albinism: evidence for a defect in an intracellular signal transduction system.
abstract: G protein-coupled receptors (GPCRs) participate in the most common signal transduction system at the plasma membrane. The wide distribution of heterotrimeric G proteins in the internal membranes suggests that a similar signalling mechanism might also be used at intracellular locations. We provide here structural evidence that the protein product of the ocular albinism type 1 gene (OA1), a pigment cell-specific integral membrane glycoprotein, represents a novel member of the GPCR superfamily and demonstrate that it binds heterotrimeric G proteins. Moreover, we show that OA1 is not found at the plasma membrane, being instead targeted to specialized intracellular organelles, the melanosomes. Our data suggest that OA1 represents the first example of an exclusively intracellular GPCR and support the hypothesis that GPCR-mediated signal transduction systems also operate at the internal membranes in mammalian cells.
authors.affiliation: Telethon Institute of Genetics and Medicine, 20132 Milan. schiaffi@tigem.it
authors.forename: M V
authors.initials: MV
authors.lastname: Schiaffino
authors.forename: M
authors.initials: M
authors.lastname: d'Addio
authors.forename: A
authors.initials: A
authors.lastname: Alloni
authors.forename: C
authors.initials: C
authors.lastname: Baschirotto
authors.forename: C
authors.initials: C
authors.lastname: Valetti
authors.forename: K
authors.initials: K
authors.lastname: Cortese
authors.forename: C
authors.initials: C
authors.lastname: Puri
authors.forename: M T
authors.initials: MT
authors.lastname: Bassi
authors.forename: C
authors.initials: C
authors.lastname: Colla
authors.forename: M
authors.initials: M
authors.lastname: De Luca
authors.forename: C
authors.initials: C
authors.lastname: Tacchetti
authors.forename: A
authors.initials: A
authors.lastname: Ballabio
mesh_terms: D016117:Albinism, Ocular / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology*; D008247:Lysosomes / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D020125:Mutation, Missense; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014162:Transfection
chemical_list: D005136:Eye Proteins; C095276:GPR143 protein, human; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D019204:GTP-Binding Proteins