title: Transport of a kinesin-cargo pair along microtubules into dendritic spines undergoing synaptic plasticity.
abstract: Synaptic plasticity often involves changes in the structure and composition of dendritic spines. Vesicular cargos and organelles enter spines either by exocytosing in the dendrite shaft and diffusing into spines or through a kinesin to myosin hand-off at the base of spines. Here we present evidence for microtubule (MT)-based targeting of a specific motor/cargo pair directly into hippocampal dendritic spines. During transient MT polymerization into spines, the kinesin KIF1A and an associated cargo, synaptotagmin-IV (syt-IV), are trafficked in unison along MTs into spines. This trafficking into selected spines is activity-dependent and results in exocytosis of syt-IV-containing vesicles in the spine head. Surprisingly, knockdown of KIF1A causes frequent fusion of syt-IV-containing vesicles throughout the dendritic shaft and diffusion into spines. Taken together, these findings suggest a mechanism for targeting dendritic cargo directly into spines during synaptic plasticity and indicate that MT-bound kinesins prevent unregulated fusion by sequestering vesicular cargo to MTs.
authors.affiliation: Department of Neuroscience, University of Wisconsin, School of Medicine and Public Health, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.
authors.forename: Derrick P
authors.initials: DP
authors.lastname: McVicker
authors.affiliation: Department of Neuroscience, University of Wisconsin, School of Medicine and Public Health, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Awe
authors.affiliation: Department of Neuroscience, University of Wisconsin, School of Medicine and Public Health, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.
authors.forename: Karl E
authors.initials: KE
authors.lastname: Richters
authors.affiliation: Department of Neuroscience, University of Wisconsin, School of Medicine and Public Health, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Wilson
authors.affiliation: Department of Neuroscience, University of Wisconsin, School of Medicine and Public Health, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.
authors.forename: Diana A
authors.initials: DA
authors.lastname: Cowdrey
authors.affiliation: Department of Neuroscience, University of Wisconsin, School of Medicine and Public Health, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.
authors.forename: Xindao
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Neuroscience, University of Wisconsin, School of Medicine and Public Health, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.|Howard Hughes Medical Institute, University of Wisconsin, School of Medicine and Public Health, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Chapman
authors.affiliation: Department of Neuroscience, University of Wisconsin, School of Medicine and Public Health, 1111 Highland Avenue, Madison, Wisconsin 53705, USA.
authors.forename: Erik W
authors.initials: EW
authors.lastname: Dent