PUBLICATION

Slc45a2 and V-ATPase are regulators of melanosomal pH homeostasis in zebrafish, providing a mechanism for human pigment evolution and disease

Authors
Dooley, C.M., Schwarz, H., Mueller, K.P., Mongera, A., Konantz, M., Neuhauss, S.C., Nüsslein-Volhard, C., and Geisler, R.
ID
ZDB-PUB-121206-42
Date
2013
Source
Pigment cell & melanoma research   26(2): 205-217 (Journal)
Registered Authors
Dooley, Christopher, Geisler, Robert, Konantz, Martina, Mongera, Alessandro, Neuhauss, Stephan, Nüsslein-Volhard, Christiane
Keywords
slc45a2, albinism, v-ATPase, melanosome, melanocyte, retinal pigment epithelium, skin color variation
MeSH Terms
  • Pigmentation*/drug effects
  • Protein Structure, Tertiary
  • Retina/drug effects
  • Retina/metabolism
  • Retina/pathology
  • Hydrogen-Ion Concentration/drug effects
  • Molecular Sequence Data
  • Humans
  • Zebrafish/metabolism*
  • Morpholinos/pharmacology
  • Biological Evolution*
  • Animals
  • Mutation/genetics
  • Membrane Transport Proteins/chemistry
  • Membrane Transport Proteins/metabolism*
  • Homeostasis*/drug effects
  • Melanophores/drug effects
  • Melanophores/metabolism
  • Melanosomes/drug effects
  • Melanosomes/metabolism*
  • Melanosomes/ultrastructure
  • Models, Biological
  • Organ Specificity/drug effects
  • Amino Acid Sequence
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/metabolism*
  • Visual Acuity/drug effects
  • Vacuolar Proton-Translocating ATPases/antagonists & inhibitors
  • Vacuolar Proton-Translocating ATPases/metabolism*
  • Cloning, Molecular
  • Alleles
  • Protein Subunits/chemistry
  • Protein Subunits/metabolism
  • Neural Crest/drug effects
  • Neural Crest/metabolism
  • Neural Crest/pathology
  • Melanocytes/metabolism
  • Melanocytes/pathology
  • Monophenol Monooxygenase/metabolism
(all 39)
PubMed
23205854 Full text @ Pigment Cell Melanoma Res.
Abstract

We present here the positional cloning of the Danio rerio albino mutant and show that the affected gene encodes Slc45a2. The human orthologous gene has previously been shown to be involved in human skin color variation and mutations therein have been implicated in the disease OCA 4. Through ultrastructural analysis of the melanosomes in albino alleles as well as the tyrosinase deficient mutant sandy we add new insights into the role of Slc45a2 in the production of melanin. In order to gain further understanding of the role of Slc45a2 and its possible interactions with other proteins involved in melanization we further analyzed the role of the V-ATPase as a melanosomal acidifier. We show that it is possible to rescue the melanization potential of the albino melanosomes through genetic and chemical inhibition of V-ATPase thereby increasing internal melanosome pH.

Genes / Markers
Figures
No images available
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b1
    Point Mutation
    b4
      Insertion
      ti225
        Unknown
        tj20e
          Unknown
          tk20
            Point Mutation
            tm83a
              Unknown
              tnr39
                Point Mutation
                tnr52
                  Small Deletion
                  w2
                    Point Mutation
                    1 - 9 of 9
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                    Human Disease / Model
                    No data available
                    Sequence Targeting Reagents
                    Fish
                    Antibodies
                    Orthology
                    Engineered Foreign Genes
                    Mapping