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

Nat Genet. 1999 Sep;23(1):108-12. doi: 10.1038/12715.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albinism, Ocular / genetics*
  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Eye Proteins / genetics
  • Eye Proteins / physiology*
  • GTP-Binding Proteins / physiology
  • Humans
  • Intracellular Membranes / physiology*
  • Lysosomes / metabolism
  • Melanocytes / cytology
  • Melanocytes / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Models, Biological
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Mutation
  • Mutation, Missense
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Transfection

Substances

  • Eye Proteins
  • GPR143 protein, human
  • Membrane Glycoproteins
  • Recombinant Proteins
  • GTP-Binding Proteins