S lc45a2 and V ‐ ATP ase are regulators of melanosomal p H homeostasis in zebrafish, providing a mechanism for human pigment evolution and disease
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Summary: We present here the positional cloning of the D anio rerio albino mutant and show that the affected gene encodes S lc45a2. 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 S lc45a2 in the production of melanin. To gain further understanding of the role of S lc45a2 and its possible interactions with other proteins involved in melanization, we further analyzed the role of the V ‐ ATP ase 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 ‐ ATP ase, thereby increasing internal melanosome p H .
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The zebrafish albino gene slc45a2 is among the highest expressed genes in each of melanocytes, RPE, and iridophores.
“We also find the zebrafish albino gene (slc45a2) to be among the highest expressed genes in each of these pigment cell types [54], [55].”
slc45a2 expression is not shared by all pigment cells, as in situ analysis reveals no enriched expression in xanthophores.
“However, in situ analysis reveals no enriched expression in xanthophores, suggesting that slc45a2 expression is not shared by all pigment cells [55].”
In mitfaw2 mutants, melanophores are missing owing to a defect in their specification; in albino mutants, melanophores are present but lack melanin.
“In mitfaw2 mutants, melanophores are missing owing to a defect in their specification; in albino mutants, melanophores are present but lack melanin27,36”
From In situ differentiation of iridophore crystallotypes underlies zebrafish stripe patterning (2020) · cites this paper as [36]
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SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans
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“Polymorphisms in the SLC45A2 locus had previously been noted to be in linkage disequilibrium when compared between Asian, African, and European populations (Graf et al., 2005, 2007).”
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Thyroid hormone regulates distinct paths to maturation in pigment cell lineages
Saunders, L. M., Mishra, A. K., Aman, A. J., Lewis, V. M., Toomey, M. B., Packer, J. S., Qiu, X., McFaline-Figueroa, J. L., Corbo, J. C., Trapnell, C., et al. (2019) · eLife · doi:10.7554/elife.45181 · Cited by 170 · see citing works
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In situ differentiation of iridophore crystallotypes underlies zebrafish stripe patterning
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- Authors
- Dooley, C. M., Schwarz, H., Mueller, K. P., Mongera, A., Konantz, M., Neuhauss, S. C. F., Nüsslein‐Volhard, C., & Geisler, R.
- Affiliations
- Max Planck Institute for Developmental Biology (DE)
- University of Zurich (CH)
- Corresponding author
- Dooley, Christopher M.
- Geisler, Robert
- ORCID
- Venue
- Pigment Cell & Melanoma Research
- Publisher
- Wiley
- Published
- 2012-12-20
- Volume
- 26
- Issue
- 2
- Pages
- 205-217
- ISSN
- 1755-1471 (ISSN-L)
- 1755-148X
- OpenAlex
- W2056355153
- Cited by
- 140
- References
- 4
- Citations by year
- 2026: 14 · 2025: 8 · 2024: 10 · 2023: 11 · 2022: 10 · 2021: 10 · 2020: 11 · 2019: 11 · 2018: 10 · 2017: 11 · 2016: 7 · 2015: 7 · 2014: 13 · 2013: 6 · 2012: 1
- FWCI
- 3.81
- Type
- journal article
- Language
- en
- Open access
- green
- zenodo.org
- Licence
- Locations
- Pigment Cell & Melanoma Research (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Funders
- European Commission
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Keywords
- SLC45A2, V-ATPase, melanogenesis, skin color variation, melanization
- MeSH terms
- Alleles, Amino Acid Sequence, Animals, Cloning, Molecular, Biological Evolution, Homeostasis, Humans, Hydrogen-Ion Concentration, Melanocytes, Melanophores, Models, Biological, Molecular Sequence Data, Mutation, Neural Crest, Organ Specificity, Pigmentation, Retina, Monophenol Monooxygenase, Visual Acuity, Zebrafish, Protein Structure, Tertiary, Melanosomes, Protein Subunits, Vacuolar Proton-Translocating ATPases, Membrane Transport Proteins, Zebrafish Proteins, Morpholinos
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