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


Dooley, Christopher M; Schwarz, Heinz; Mueller, Kaspar P; Mongera, Alessandro; Konantz, Martina; Neuhauss, Stephan C F; Nüsslein-Volhard, Christiane; Geisler, Robert (2013). Slc45a2 and V-ATPase are regulators of melanosomal pH homeostasis in zebrafish, providing a mechanism for human pigment evolution and disease. Pigment Cell & Melanoma Research, 26(2):205-217.

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.

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.

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32 citations in Web of Science®
34 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Uncontrolled Keywords:slc45a2; albinism; V-ATPase; melanosome; melanocyte; retinal pigment epithelium; skin color variation
Language:English
Date:2013
Deposited On:16 Jan 2013 11:48
Last Modified:05 Apr 2016 16:16
Publisher:Wiley-Blackwell
ISSN:1755-1471
Publisher DOI:https://doi.org/10.1111/pcmr.12053
PubMed ID:23205854

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