title: Myosin Va binding to neurofilaments is essential for correct myosin Va distribution and transport and neurofilament density.
abstract: The identification of molecular motors that modulate the neuronal cytoskeleton has been elusive. Here, we show that a molecular motor protein, myosin Va, is present in high proportions in the cytoskeleton of mouse CNS and peripheral nerves. Immunoelectron microscopy, coimmunoprecipitation, and blot overlay analyses demonstrate that myosin Va in axons associates with neurofilaments, and that the NF-L subunit is its major ligand. A physiological association is indicated by observations that the level of myosin Va is reduced in axons of NF-L-null mice lacking neurofilaments and increased in mice overexpressing NF-L, but unchanged in NF-H-null mice. In vivo pulse-labeled myosin Va advances along axons at slow transport rates overlapping with those of neurofilament proteins and actin, both of which coimmunoprecipitate with myosin Va. Eliminating neurofilaments from mice selectively accelerates myosin Va translocation and redistributes myosin Va to the actin-rich subaxolemma and membranous organelles. Finally, peripheral axons of dilute-lethal mice, lacking functional myosin Va, display selectively increased neurofilament number and levels of neurofilament proteins without altering axon caliber. These results identify myosin Va as a neurofilament-associated protein, and show that this association is essential to establish the normal distribution, axonal transport, and content of myosin Va, and the proper numbers of neurofilaments in axons.
authors.affiliation: Center for Dementia Research, Nathan Kline Institute, NYU School of Medicine, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA.
authors.forename: Mala V
authors.initials: MV
authors.lastname: Rao
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Engle
authors.forename: Panaiyur S
authors.initials: PS
authors.lastname: Mohan
authors.forename: Aidong
authors.initials: A
authors.lastname: Yuan
authors.forename: Dike
authors.initials: D
authors.lastname: Qiu
authors.forename: Anne
authors.initials: A
authors.lastname: Cataldo
authors.forename: Linda
authors.initials: L
authors.lastname: Hassinger
authors.forename: Stephen
authors.initials: S
authors.lastname: Jacobsen
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.forename: Athena
authors.initials: A
authors.lastname: Andreadis
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Julien
authors.forename: Paul C
authors.initials: PC
authors.lastname: Bridgman
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Nixon
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D001419:Bacteria; D003599:Cytoskeleton / Q000378:metabolism; D007382:Intermediate Filaments / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D020409:Molecular Motor Proteins / Q000378:metabolism; D024701:Myosin Type V / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012584:Sciatic Nerve / Q000378:metabolism
chemical_list: D020409:Molecular Motor Proteins; D016900:Neurofilament Proteins; D011993:Recombinant Fusion Proteins; C044882:neurofilament protein L; D024701:Myosin Type V