title: Oculocutaneous albinism: developing novel antibodies targeting the proteins associated with OCA2 and OCA4.
abstract: BACKGROUND
  Patients with oculocutaneous albinism (OCA) have severely decreased pigmentation of their skin, hair and eyes. OCA2 and OCA4 result from mutations of the OCA2 and SLC45A2 genes, respectively, both of which disrupt the trafficking of the critical melanogenic enzyme tyrosinase to melanosomes. Both proteins encoded by those loci (termed P and MATP, respectively) have 12 putative transmembrane regions and are thought to function as transporters, although their functions and subcellular localizations remain to be characterized.
  
  
  OBJECTIVE
  To generate specific antibodies against unique synthetic peptides encoded by P and MATP that could be used to characterize their functions and subcellular localizations.
  
  
  METHODS
  Western blotting and immunohistochemistry were used to assess the specificity of antibodies and to colocalize P and MATP proteins with various subcellular markers.
  
  
  RESULTS
  Specific antibodies to the P and MATP proteins were generated that work well for Western blotting and immunohistochemistry. The localizations of P and MATP with various subcellular organelles were characterized using confocal microscopy, which revealed that they colocalize to some extent with LAMP2, but do not significantly colocalize with markers of the ER, Golgi or melanosomes. Interestingly, both P and MATP colocalize significantly with BLOC-1, a sorting component involved in the intracellular trafficking of melanosomal/lysosomal constituents.
  
  
  CONCLUSIONS
  These results provide a basis to understand how disrupted functions of P or MATP result in the misrouting of tyrosinase and cause the hypopigmentation seen in OCA2 and OCA4.
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Namiki
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Sergio G
authors.initials: SG
authors.lastname: Coelho
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Valencia
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: hearingv@nih.gov.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Hearing
mesh_terms: D016115:Albinism, Oculocutaneous / Q000276:immunology*; D000595:Amino Acid Sequence; D000906:Antibodies / Q000737:chemistry*; D000951:Antigens, Neoplasm / Q000378:metabolism; D001692:Biological Transport; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D017496:Hypopigmentation / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008544:Melanocytes / Q000166:cytology; D020460:Melanosomes / Q000276:immunology / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000276:immunology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; C104378:BLOC1S1 protein, human; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C489600:OCA2 protein, human; D010455:Peptides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C510061:SLC45A2 protein, human; D014442:Monophenol Monooxygenase
keywords: Albinism; BLOC-1; MATP protein; OCA2; OCA4; P protein