Journal article
Cell Death of Melanophores in Zebrafish trpm7 Mutant Embryos Depends on Melanin Synthesis
Journal of investigative dermatology, Vol.127(8), pp.2020-2030
08/2007
DOI: 10.1038/sj.jid.5700710
PMID: 17290233
Abstract
Transient receptor potential melastatin 7 (TRPM7) is a broadly expressed, non-selective cation channel. Studies in cultured cells implicate TRPM7 in regulation of cell growth, spreading, and survival. However, zebrafish trpm7 homozygous mutants display death of melanophores and temporary paralysis, but no gross morphological defects during embryonic stages. This phenotype implies that melanophores are unusually sensitive to decreases in Trpm7 levels, a hypothesis we investigate here. We find that pharmacological inhibition of caspases does not rescue melanophore viability in trpm7 mutants, implying that melanophores die by a mechanism other than apoptosis. Consistent with this possibility, ultrastructural analysis of dying melanophores in trpm7 mutants reveals abnormal melanosomes and evidence of a ruptured plasma membrane, indicating that cell death occurs by necrosis. Interestingly, inhibition of melanin synthesis largely prevents melanophore cell death in trpm7 mutants. These results suggest that melanophores require Trpm7 in order to detoxify intermediates of melanin synthesis. We find that unlike TRPM1, TRPM7 is expressed in human melanoma cell lines, indicating that these cells may also be sensitized to reduction of TRPM7 levels.
Details
- Title: Subtitle
- Cell Death of Melanophores in Zebrafish trpm7 Mutant Embryos Depends on Melanin Synthesis
- Creators
- Matthew S McNeill - Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, USAJennifer Paulsen - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USAGregory Bonde - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USAErin Burnight - Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, Iowa, USAMei-Yu Hsu - Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USARobert A Cornell - Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Journal of investigative dermatology, Vol.127(8), pp.2020-2030
- Publisher
- Elsevier Inc
- DOI
- 10.1038/sj.jid.5700710
- PMID
- 17290233
- ISSN
- 0022-202X
- eISSN
- 1523-1747
- Language
- English
- Date published
- 08/2007
- Academic Unit
- Anatomy and Cell Biology; Dental Research; Ophthalmology and Visual Sciences
- Record Identifier
- 9984025370102771
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