McVicker Derrick P, Awe Adam M, Richters Karl E, Wilson Rebecca L, Cowdrey Diana A, Hu Xindao, Chapman Edwin R, Dent Erik W
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.
Nat Commun. 2016 Sep 23;7:12741. doi: 10.1038/ncomms12741.
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.
突触可塑性通常涉及树突棘的结构和组成变化。囊泡货物和细胞器进入树突棘的方式，要么是在树突干中通过胞吐作用扩散到树突棘中，要么是通过驱动蛋白在树突棘基部与肌球蛋白交接。在这里，我们提供了基于微管（MT）将特定的马达蛋白/货物对直接靶向海马体树突棘的证据。在微管短暂聚合进入树突棘的过程中，驱动蛋白KIF1A和相关货物突触结合蛋白IV（syt-IV）沿着微管一起运输到树突棘中。这种向选定树突棘的运输是依赖于活动的，并导致含syt-IV的囊泡在树突棘头部胞吐。令人惊讶的是，敲低KIF1A会导致含syt-IV的囊泡在整个树突干中频繁融合并扩散到树突棘中。综上所述，这些发现揭示了在突触可塑性过程中将树突货物直接靶向树突棘的一种机制，并表明与微管结合的驱动蛋白通过将囊泡货物隔离在微管上来防止不受调控的融合。
