Functional interactions between OCA2 and the protein complexes BLOC-1, BLOC-2, and AP-3 inferred from epistatic analyses of mouse coat pigmentation

Pigment Cell Melanoma Res. 2011 Apr;24(2):275-81. doi: 10.1111/j.1755-148X.2010.00815.x. Epub 2010 Dec 17.

Abstract

The biogenesis of melanosomes is a multistage process that requires the function of cell-type-specific and ubiquitously expressed proteins. OCA2, the product of the gene defective in oculocutaneous albinism type 2, is a melanosomal membrane protein with restricted expression pattern and a potential role in the trafficking of other proteins to melanosomes. The ubiquitous protein complexes AP-3, BLOC-1, and BLOC-2, which contain as subunits the products of genes defective in various types of Hermansky-Pudlak syndrome, have been likewise implicated in trafficking to melanosomes. We have tested for genetic interactions between mutant alleles causing deficiency in OCA2 (pink-eyed dilution unstable), AP-3 (pearl), BLOC-1 (pallid), and BLOC-2 (cocoa) in C57BL/6J mice. The pallid allele was epistatic to pink-eyed dilution, and the latter behaved as a semi-dominant phenotypic enhancer of cocoa and, to a lesser extent, of pearl. These observations suggest functional links between OCA2 and these three protein complexes involved in melanosome biogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albinism, Oculocutaneous / genetics
  • Albinism, Oculocutaneous / metabolism
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Color
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Epistasis, Genetic*
  • Female
  • Hair / metabolism*
  • Hermanski-Pudlak Syndrome / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Lectins / genetics
  • Lectins / metabolism*
  • Male
  • Melanins / metabolism
  • Mice
  • Mutation
  • Pigmentation / genetics*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Vesicular Transport Proteins

Substances

  • Bloc1s6 protein, mouse
  • Carrier Proteins
  • DNA-Binding Proteins
  • Hps6 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Lectins
  • Melanins
  • Transcription Factors
  • Vesicular Transport Proteins
  • enhancer-binding protein AP-3

Supplementary concepts

  • Oculocutaneous albinism type 2