Zebrafish Melanophilin Facilitates Melanosome Dispersion by Regulating Dynein

Lavinia Sheets, David G. Ransom, Eve M. Mellgren, Stephen L. Johnson, Bruce J. Schnapp

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Background: Fish melanocytes aggregate or disperse their melanosomes in response to the level of intracellular cAMP. The role of cAMP is to regulate both melanosome travel along microtubules and their transfer between microtubules and actin. The factors that are downstream of cAMP and that directly modulate the motors responsible for melanosome transport are not known. To identify these factors, we are characterizing melanosome transport mutants in zebrafish. Results: We report that a mutation (allele j120) in the gene encoding zebrafish melanophilin (Mlpha) interferes with melanosome dispersion downstream of cAMP. Based on mouse genetics, the current model of melanophilin function is that melanophilin links myosin V to melanosomes. The residues responsible for this function are conserved in the zebrafish ortholog. However, if linking myosin V to melanosomes was Mlpha's sole function, elevated cAMP would cause mlphaj120 mutant melanocytes to hyperdisperse their melanosomes. Yet this is not what we observe. Instead, mutant melanocytes disperse their melanosomes much more slowly than normal and less than halfway to the cell margin. This defect is caused by a failure to suppress minus-end (dynein) motility along microtubules, as shown by tracking individual melanosomes. Disrupting the actin cytoskeleton, which causes wild-type melanocytes to hyperdisperse their melanosomes, does not affect dispersion in mutant melanocytes. Therefore, Mlpha regulates dynein independently of its putative linkage to myosin V. Conclusions: We propose that cAMP-induced melanosome dispersion depends on the actin-independent suppression of dynein by Mlpha and that Mlpha coordinates the early outward movement of melanosomes along microtubules and their later transfer to actin filaments.

Original languageEnglish (US)
Pages (from-to)1721-1734
Number of pages14
JournalCurrent Biology
Volume17
Issue number20
DOIs
StatePublished - Oct 23 2007

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Keywords

  • CELLBIO

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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