磷酸肌醇 4-磷酸 5-激酶α（PIPKα）调节神经元微管解聚酶驱动蛋白 KIF2A，并抑制轴突分支的伸长。
Phosphatidylinositol 4-phosphate 5-kinase alpha (PIPKα) regulates neuronal microtubule depolymerase kinesin, KIF2A and suppresses elongation of axon branches.
机构信息
Department of Cell Biology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
出版信息
Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):1725-30. doi: 10.1073/pnas.1107808109. Epub 2012 Jan 17.
Abstract
Neuronal morphology is regulated by cytoskeletons. Kinesin superfamily protein 2A (KIF2A) depolymerizes microtubules (MTs) at growth cones and regulates axon pathfinding. The factors controlling KIF2A in neurite development remain totally elusive. Here, using immunoprecipitation with an antibody specific to KIF2A, we identified phosphatidylinositol 4-phosphate 5-kinase alpha (PIPKα) as a candidate membrane protein that regulates the activity of KIF2A. Yeast two-hybrid and biochemical assays demonstrated direct binding between KIF2A and PIPKα. Partial colocalization of the clusters of punctate signals for these two molecules was detected by confocal microscopy and photoactivated localization microscopy. Additionally, the MT-depolymerizing activity of KIF2A was enhanced in the presence of PIPKα in vitro and in vivo. PIPKα suppressed the elongation of axon branches in a KIF2A-dependent manner, suggesting a unique PIPK-mediated mechanism controlling MT dynamics in neuronal development.
摘要
神经元形态由细胞骨架调节。驱动蛋白超家族蛋白 2A（KIF2A）在生长锥处解聚微管（MTs），并调节轴突寻路。控制神经突发育过程中 KIF2A 的因素仍然完全难以捉摸。在这里，我们使用针对 KIF2A 的抗体进行免疫沉淀，鉴定出磷脂酰肌醇 4-磷酸 5-激酶α（PIPKα）作为调节 KIF2A 活性的候选膜蛋白。酵母双杂交和生化分析表明 KIF2A 和 PIPKα 之间存在直接结合。通过共聚焦显微镜和光活化定位显微镜检测到这两个分子的点状信号簇的部分共定位。此外，体外和体内实验均表明 PIPKα 增强了 KIF2A 的 MT 解聚活性。PIPKα 以依赖于 KIF2A 的方式抑制轴突分支的伸长，表明 PIPK 介导的机制在神经元发育中控制 MT 动力学具有独特性。
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