title: Stable kinesin and dynein assemblies drive the axonal transport of mammalian prion protein vesicles.
abstract: Kinesin and dynein are opposite-polarity microtubule motors that drive the tightly regulated transport of a variety of cargoes. Both motors can bind to cargo, but their overall composition on axonal vesicles and whether this composition directly modulates transport activity are unknown. Here we characterize the intracellular transport and steady-state motor subunit composition of mammalian prion protein (PrP(C)) vesicles. We identify Kinesin-1 and cytoplasmic dynein as major PrP(C) vesicle motor complexes and show that their activities are tightly coupled. Regulation of normal retrograde transport by Kinesin-1 is independent of dynein-vesicle attachment and requires the vesicle association of a complete Kinesin-1 heavy and light chain holoenzyme. Furthermore, motor subunits remain stably associated with stationary as well as with moving vesicles. Our data suggest a coordination model wherein PrP(C) vesicles maintain a stable population of associated motors whose activity is modulated by regulatory factors instead of by structural changes to motor-cargo associations.
authors.affiliation: Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, 92093, USA. sencalada@ucsd.edu
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Encalada
authors.forename: Lukasz
authors.initials: L
authors.lastname: Szpankowski
authors.forename: Chun-hong
authors.initials: CH
authors.lastname: Xia
authors.forename: Lawrence S B
authors.initials: LS
authors.lastname: Goldstein
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D009474:Neurons / Q000378:metabolism; D018621:PrPC Proteins / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: D018621:PrPC Proteins; D004398:Dyneins; D016547:Kinesins