Slac2-a/melanophilin, the missing link between Rab27 and myosin Va: Implications of a tripartite protein complex for melanosome transport

Mitsunori Fukuda, Taruho S. Kuroda, Katsuhiko Mikoshiba

Research output: Contribution to journalArticlepeer-review

277 Citations (Scopus)

Abstract

Myosin Va is a member of the unconventional class V myosin family, and a mutation in the myosin Va gene causes pigment granule transport defects in human Griscelli syndrome and dilute mice. How myosin Va recognizes its cargo (i.e. melanosomes), however, has remained undetermined over the past decade. In this study, we discovered Slac2-a/melanophilin to be the "missing link" between myosin Va and GTP-Rab27A present in the melanosome. Deletion analysis and site-directed mutagenesis showed that the N-terminal Sip Slp (synaptotagmin-like protein) homology domain of Slac2-a specifically binds Rab27AfB Rab27AIB isoforms and that the C-terminal half directly binds the globular tail of myosin Va. The tripartite protein complex (Rab27A.-Slac2-a.myosin a-myosin Va) in melanoma cells was further confirmed by immunoprecipitation. The discovery that myosin Va indirectly recognizes its cargo through Slac2-a, a novel Rab27A/B effector, should shed light on molecular recognition of its specific cargo by class V myosin.

Original languageEnglish
Pages (from-to)12432-12436
Number of pages5
JournalJournal of Biological Chemistry
Volume277
Issue number14
DOIs
Publication statusPublished - 2002 Apr 5
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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