Homma Noriko, Takei Yosuke, Tanaka Yosuke, Nakata Takao, Terada Sumio, Kikkawa Masahide, Noda Yasuko, Hirokawa Nobutaka
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Hongo Bunkyo-ku, Tokyo 113-0033, Japan.
Cell. 2003 Jul 25;114(2):229-39. doi: 10.1016/s0092-8674(03)00522-1.
Through interactions with microtubules, the kinesin superfamily of proteins (KIFs) could have multiple roles in neuronal function and development. During neuronal development, postmitotic neurons develop primary axons extending toward targets, while other collateral branches remain short. Although the process of collateral branching is important for correct wiring of the brain, the mechanisms involved are not well understood. In this study, we analyzed kif2a(-/-) mice, whose brains showed multiple phenotypes, including aberrant axonal branching due to overextension of collateral branches. In kif2a(-/-) growth cones, microtubule-depolymerizing activity decreased. Moreover, many individual microtubules showed abnormal behavior at the kif2a(-/-) cell edge. Based on these results, we propose that KIF2A regulates microtubule dynamics at the growth cone edge by depolymerizing microtubules and that it plays an important role in the suppression of collateral branch extension.
通过与微管相互作用,驱动蛋白超家族(KIFs)可能在神经元功能和发育中发挥多种作用。在神经元发育过程中,有丝分裂后的神经元长出向靶标延伸的初级轴突,而其他侧支则保持较短。尽管侧支分支过程对于大脑的正确布线很重要,但其涉及的机制尚未完全了解。在本研究中,我们分析了kif2a(-/-)小鼠,其大脑表现出多种表型,包括由于侧支过度延伸导致的异常轴突分支。在kif2a(-/-)生长锥中,微管解聚活性降低。此外,许多单个微管在kif2a(-/-)细胞边缘表现出异常行为。基于这些结果,我们提出KIF2A通过解聚微管来调节生长锥边缘的微管动力学,并且它在抑制侧支延伸中起重要作用。