Midorikawa Ryosuke, Takei Yosuke, Hirokawa Nobutaka
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Tokyo 113-0033, Japan.
Cell. 2006 Apr 21;125(2):371-83. doi: 10.1016/j.cell.2006.02.039.
In brain development, apoptosis is a physiological process that controls the final numbers of neurons. Here, we report that the activity-dependent prevention of apoptosis in juvenile neurons is regulated by kinesin superfamily protein 4 (KIF4), a microtubule-based molecular motor. The C-terminal domain of KIF4 is a module that suppresses the activity of poly (ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme known to maintain cell homeostasis by repairing DNA and serving as a transcriptional regulator. When neurons are stimulated by membrane depolarization, calcium signaling mediated by CaMKII induces dissociation of KIF4 from PARP-1, resulting in upregulation of PARP-1 activity, which supports neuron survival. After dissociation from PARP-1, KIF4 enters into the cytoplasm from the nucleus and moves to the distal part of neurites in a microtubule-dependent manner. We suggested that KIF4 controls the activity-dependent survival of postmitotic neurons by regulating PARP-1 activity in brain development.
在大脑发育过程中，细胞凋亡是控制神经元最终数量的生理过程。在此，我们报告，幼年神经元中依赖活动的凋亡预防由驱动蛋白超家族蛋白4（KIF4）调控，KIF4是一种基于微管的分子马达。KIF4的C端结构域是一个抑制聚（ADP - 核糖）聚合酶-1（PARP - 1）活性的模块，PARP - 1是一种核酶，已知其通过修复DNA和作为转录调节因子来维持细胞内稳态。当神经元受到膜去极化刺激时，由CaMKII介导的钙信号传导诱导KIF4与PARP - 1解离，导致PARP - 1活性上调，从而支持神经元存活。从PARP - 1解离后，KIF4从细胞核进入细胞质，并以微管依赖的方式移动到神经突的远端。我们认为，KIF4在大脑发育过程中通过调节PARP - 1活性来控制有丝分裂后神经元的依赖活动的存活。
