Institut de Génétique et de Biologie Moléculaire et Cellulaire, IGBMC, 67404 Illkirch, France; Centre National de la Recherche Scientifique, CNRS, UMR7104, 67404 Illkirch, France; Institut National de la Santé et de la Recherche Médicale, INSERM, U1258, 67404 Illkirch, France; Université de Strasbourg, 67000 Strasbourg, France.
Université de Strasbourg, 67000 Strasbourg, France; Laboratoire de Bioimagerie et Pathologies, Centre National de la Recherche Scientifique, UMR 7021, 67404 Illkirch, France.
Cell Rep. 2023 Jul 25;42(7):112744. doi: 10.1016/j.celrep.2023.112744. Epub 2023 Jul 6.
Completion of neuronal migration is critical for brain development. Kif21b is a plus-end-directed kinesin motor protein that promotes intracellular transport and controls microtubule dynamics in neurons. Here we report a physiological function of Kif21b during radial migration of projection neurons in the mouse developing cortex. In vivo analysis in mouse and live imaging on cultured slices demonstrate that Kif21b regulates the radial glia-guided locomotion of newborn neurons independently of its motility on microtubules. We show that Kif21b directly binds and regulates the actin cytoskeleton both in vitro and in vivo in migratory neurons. We establish that Kif21b-mediated regulation of actin cytoskeleton dynamics influences branching and nucleokinesis during neuronal locomotion. Altogether, our results reveal atypical roles of Kif21b on the actin cytoskeleton during migration of cortical projection neurons.
神经元迁移的完成对大脑发育至关重要。Kif21b 是一种正向驱动的驱动蛋白马达蛋白，可促进细胞内运输并控制神经元中的微管动力学。在这里，我们报告了 Kif21b 在小鼠发育皮层中的投射神经元放射状迁移过程中的生理功能。在小鼠中的体内分析和培养切片上的实时成像表明，Kif21b 独立于其在微管上的运动，调节新生神经元的放射状神经胶质引导的运动。我们表明，Kif21b 直接结合并调节体外和体内迁移神经元中的肌动蛋白细胞骨架。我们确定 Kif21b 介导的肌动蛋白细胞骨架动力学的调节会影响神经元运动过程中的分支和核迁移。总之，我们的结果揭示了 Kif21b 在皮质投射神经元迁移过程中对肌动蛋白细胞骨架的非典型作用。
