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Identification of an organelle receptor for myosin-Va

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.

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Figure 1: Myosin-Va-dependent melanosome capture is disabled in leaden melanocytes and restored by reintroducing melanophilin.
Figure 2: The recruitment of endogenous and exogenous myosin-Va to the melanosome surface is dependent on melanophilin.
Figure 3: Melanophilin is absent from both leaden and ashen melanocytes and binds to beads coated with purified myosin-Va in an exon-F-dependent fashion.
Figure 4: Melanophilin is a melanosome-associated protein.
Figure 5: Hierarchy of melanosome targeting for myosin-Va, melanophilin, and Rab27a.
Figure 6: Melanophilin bridges the indirect interaction between myosin-Va and Rab27a.
Figure 7: Deleting either the N- and C-terminal domain of melanophilin creates a leaden-like phenotype in wild-type melanocytes.
Figure 8: Organization of the melanosome receptor for myosin-Va.

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Wu, X., Rao, K., Zhang, H. et al. Identification of an organelle receptor for myosin-Va. Nat Cell Biol 4, 271–278 (2002). https://doi.org/10.1038/ncb760

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