ZFIN ID: ZDB-PUB-070302-2
Cell Death of Melanophores in Zebrafish trpm7 Mutant Embryos Depends on Melanin Synthesis
McNeill, M.S., Paulsen, J., Bonde, G., Burnight, E., Hsu, M.Y., and Cornell, R.A.
Date: 2007
Source: The Journal of investigative dermatology   127(8): 2020-30 (Journal)
Registered Authors: Bonde, Greg, Cornell, Robert
Keywords: none
MeSH Terms:
  • Animals
  • Apoptosis
  • Caspase Inhibitors
  • Cell Line, Tumor
  • Cell Survival
  • Embryo, Nonmammalian/cytology
  • Magnesium/pharmacology
  • Melanins/biosynthesis*
  • Melanoma/chemistry
  • Melanophores/cytology*
  • Mutation
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-kit/physiology
  • TRPM Cation Channels/analysis
  • TRPM Cation Channels/genetics
  • TRPM Cation Channels/physiology*
  • Tumor Suppressor Protein p53/antagonists & inhibitors
  • Tumor Suppressor Protein p53/physiology
  • Zebrafish
  • Zebrafish Proteins/analysis
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed: 17290233 Full text @ J. Invest. Dermatol.
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.