Ocular albinism: evidence for a defect in an intracellular signal transduction system

@article{Schiaffino1999OcularAE,
  title={Ocular albinism: evidence for a defect in an intracellular signal transduction system},
  author={Maria Vittoria Schiaffino and Marilena d'Addio and Anna Alloni and Cinzia Baschirotto and Caterina Valetti and Katia Cortese and Claudia Puri and Maria Teresa Bassi and Cristina Colla and Michele De Luca and Carlo Tacchetti and Andrea Ballabio},
  journal={Nature Genetics},
  year={1999},
  volume={23},
  pages={108-112}
}
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… 
The ocular albinism type 1 (OA1) protein and the evidence for an intracellular signal transduction system involved in melanosome biogenesis.
TLDR
These findings support previous hypotheses that GPCR-mediated signaling might also operate at the internal membranes in mammalian cells and 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.
The melanosomal/lysosomal protein OA1 has properties of a G protein-coupled receptor.
TLDR
These findings indicate that heterologously expressed OA1 exhibits two fundamental properties of GPCRs, being capable to activate heterotrimeric G proteins and to functionally associate with arrestins, and provide proof of principle that OA 1 can actually function as a canonical GPCR in mammalian cells.
The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells
TLDR
The results enlighten a novel function for OA1 in pigment cells and suggest that ocular albinism type 1 might result from a different pathogenetic mechanism than previously thought, based on an organelle-autonomous signalling pathway implicated in the regulation of both membrane traffic and transport.
Structural insights into human GPCR protein OA1: a computational perspective
TLDR
Homology modeling was applied to predicting OA1 structure following thorough sequence analysis and secondary structure predictions, and the predicted model had the signature residues and motifs expected of GPCRs, and was used for carrying out molecular docking studies with an endogenous ligand and an antagonist; the results agreed quite well with the available experimental data.
The Many Faces of G Protein-Coupled Receptor 143, an Atypical Intracellular Receptor
TLDR
G protein-coupled receptor 143 (GPR143), an enigmatic receptor in terms of classification within the GPCR superfamily and localization, is introduced and the most important motifs of classes A and B are described and compared to the protein sequence of GPR143.
The ocular albinism type 1 (OA1) G-protein-coupled receptor functions with MART-1 at early stages of melanogenesis to control melanosome identity and composition.
TLDR
Analysis of siRNA inactivation and combined morphological and biochemical methods show for the first time that melanosome composition and identity are regulated at early stages by OA1 and that MART-1 likely acts as an escort protein for this GPCR.
The mouse ocular albinism 1 gene product is an endolysosomal protein.
TLDR
Results indicate that Oa1 is a melanocyte-specific integral membrane glycoprotein localized to late endosomes/lysosomes but not mature melanosomes, and speculate that OA1 may play a role in the trafficking of vesicles to developing melanosome.
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TLDR
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