Guillaud Laurent, Wong Richard, Hirokawa Nobutaka
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Nat Cell Biol. 2008 Jan;10(1):19-29. doi: 10.1038/ncb1665. Epub 2007 Dec 9.
Establishment and maintenance of cell structures and functions are highly dependent on the efficient regulation of intracellular transport in which proteins of the kinesin superfamily (KIFs) are very important. In this regard, how KIFs regulate the release of their cargo is a critical process that remains to be elucidated. To address this specific question, we have investigated the mechanism behind the regulation of the KIF17-Mint1 interaction. Here we report that the tail region of the molecular motor KIF17 is regulated by phosphorylation. Using direct visualization of protein-protein interaction by FRET and various in vitro and in vivo approaches we have demonstrated that CaMKII-dependent phosphorylation of KIF17 on Ser 1029 disrupts the KIF17-Mint1 association and results in the release of the transported cargo from its microtubule-based transport.
细胞结构和功能的建立与维持高度依赖于细胞内运输的有效调控，其中驱动蛋白超家族（KIFs）的蛋白质非常重要。在这方面，KIFs如何调节其货物的释放是一个仍有待阐明的关键过程。为了解决这个具体问题，我们研究了KIF17-Mint1相互作用调控背后的机制。在此我们报告，分子马达KIF17的尾部区域受磷酸化调控。通过荧光共振能量转移（FRET）对蛋白质-蛋白质相互作用进行直接可视化，并采用各种体外和体内方法，我们证明了KIF17在Ser 1029位点的CaMKII依赖性磷酸化破坏了KIF17-Mint1的结合，并导致所运输的货物从基于微管的运输中释放出来。
