Nature Cell Biology
4, 271 - 278 (2002)
Published online: 4 March 2002; | doi:10.1038/ncb760
Identification of an organelle receptor for myosin-VaXufeng S. Wu1, Kang Rao1, Hong Zhang1, Fei Wang2, James R. Sellers2, Lydia E. Matesic3, Neal G. Copeland3, Nancy A. Jenkins3
& John A. Hammer III1, 41
Laboratory of Cell Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
2
Laboratory of Molecular Cardiology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
3
Mouse Cancer Genetics Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
4
hammerj@nhlbi.nih.gov
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.
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