Identification of an organelle receptor for myosin-Va

Xufeng S. Wu, Kang Rao, Hong Zhang, Fei Wang, James R. Sellers, Lydia E. Matesic, Neal G. Copeland, Nancy A. Jenkins, John A. Hammer

Research output: Contribution to journalArticle

362 Scopus citations

Abstract

Little is known about how molecular motors bind to their vesicular cargo. Here we show that myosin-Va, an actin-based vesicle motor, binds to one of its cargoes, the melanosome, by interacting with a receptor-protein complex containing Rab27a and melanophilin, a postulated Rab27a effector. Rab27a binds to the melanosome first and then recruits melanophilin, which in turn recruits myosin-Va. Melanophilin creates this link by binding to Rab27a in a GTP-dependent fashion through its amino terminus, and to myosin-Va through its carboxy terminus. Moreover, this latter interaction, similar to the ability of myosin-Va to colocalize with melanosomes and influence their distribution in vivo, is absolutely dependent on the presence of exon-F, an alternatively spliced exon in the myosin-Va tail. These results provide the first molecular description of an organelle receptor for an actin-based motor, illustrate how alternate exon usage can be used to specify cargo, and further expand the functional repertoire of Rab GTPases and their effectors.

Original languageEnglish (US)
Pages (from-to)271-278
Number of pages8
JournalNature Cell Biology
Volume4
Issue number4
DOIs
StatePublished - Apr 2002

ASJC Scopus subject areas

  • Cell Biology

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