title: Cargo binding activates myosin VIIA motor function in cells.
abstract: Myosin VIIA, thought to be involved in human auditory function, is a gene responsible for human Usher syndrome type 1B, which causes hearing and visual loss. Recent studies have suggested that it can move processively if it forms a dimer. Nevertheless, it exists as a monomer in vitro, unlike the well-known two-headed processive myosin Va. Here we studied the molecular mechanism, which is currently unknown, of activating myosin VIIA as a cargo-transporting motor. Human myosin VIIA was present throughout cytosol, but it moved to the tip of filopodia upon the formation of dimer induced by dimer-inducing reagent. The forced dimer of myosin VIIA translocated its cargo molecule, MyRip, to the tip of filopodia, whereas myosin VIIA without the forced dimer-forming module does not translocate to the filopodial tips. These results suggest that dimer formation of myosin VIIA is important for its cargo-transporting activity. On the other hand, myosin VIIA without the forced dimerization module became translocated to the filopodial tips in the presence of cargo complex, i.e., MyRip/Rab27a, and transported its cargo complex to the tip. Coexpression of MyRip promoted the association of myosin VIIA to vesicles and the dimer formation. These results suggest that association of myosin VIIA monomers with membrane via the MyRip/Rab27a complex facilitates the cargo-transporting activity of myosin VIIA, which is achieved by cluster formation on the membrane, where it possibly forms a dimer. Present findings support that MyRip, a cargo molecule, functions as an activator of myosin VIIA transporter function.
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sakai
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Umeki
authors.forename: Reiko
authors.initials: R
authors.lastname: Ikebe
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Ikebe
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004789:Enzyme Activation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D011554:Pseudopodia / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000075745:rab27 GTP-Binding Proteins
chemical_list: C000631455:MYO7A protein, human; C501262:MYRIP protein, human; D046912:Multiprotein Complexes; D000081412:Myosin VIIa; D033921:Vesicular Transport Proteins; D000075745:rab27 GTP-Binding Proteins; C066694:RAB27A protein, human; D009218:Myosins; D020691:rab GTP-Binding Proteins