Identification of an organelle receptor for myosin-Va

XS Wu, K Rao, H Zhang, F Wang, JR Sellers… - Nature cell …, 2002 - nature.com
XS Wu, K Rao, H Zhang, F Wang, JR Sellers, LE Matesic, NG Copeland, NA Jenkins…
Nature cell biology, 2002nature.com
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 …
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.
nature.com