Phosphorylation of CRMP2 is required for migration and positioning of Purkinje cells: Redundant roles of CRMP1 and CRMP4
Phosphorylation of CRMP2 is required for migration and positioning of Purkinje cells: Redundant roles of CRMP1 and CRMP4
复制标题
浦肯野细胞的迁移和定位需要 CRMP2 的磷酸化：CRMP1 和 CRMP4 的冗余作用
DOI：
10.1016/j.brainres.2020.146762
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发表时间：
2020
期刊：
影响因子：
2.9
通讯作者：
Ohshima Toshio
中科院分区：
文献类型：
--
作者：
Yamazaki Yuki;Nagai Jun;Akinaga Satoshi;Koga Yumeno;Hasegawa Masaya;Takahashi Miyuki;Yamashita Naoya;Kolattukudy Papachan;Goshima Yoshio;Ohshima Toshio
浦肯野细胞的正确迁移和定位对发育中小脑的形成至关重要。虽然已知几种细胞周期蛋白依赖性激酶5（cyclin-dependent kinase 5，Cdk 5）底物对有序的神经元迁移至关重要，但目前还没有基于突变小鼠的体内研究Cdk 5磷酸化底物在浦肯野细胞迁移中的功能的报道。因为先前的研究报道了通过shRNA介导的CRMP 2敲低导致皮质神经元迁移缺陷。然而，CRMP 2 KI/KI小鼠，其中Cdk 5-磷酸化被抑制，显示浦肯野细胞迁移和定位的小缺陷。我们假设其他CRMPs的代偿冗余功能，并分析了CRMP 1敲除（KO）、CRMP 2 KI/KI和CRMP 4 KO小鼠小脑中浦肯野细胞的迁移和定位。在三突变小鼠中观察到浦肯野细胞的迁移和定位的严重障碍。我们还发现了三重CRMPs突变小鼠的运动协调缺陷。这些结果表明，CRMP 2的磷酸化Cdk 5和CRMP 1和CRMP 4的冗余功能，在适当的迁移和浦肯野细胞在小脑发育定位的重要性。
Proper migration and positioning of Purkinje cells are important for formation of the developing cerebellum. Although several cyclin-dependent kinase 5 (Cdk5) substrates are known to be critical for ordered neuronal migration, there are no reports of mutant mouse-based, in vivo studies on the function of Cdk5-phosphorylation substrates in migration of Purkinje cells.We focused on the analysis of collapsin response mediator protein 2 (CRMP2), one of the Cdk5 substrates, because a previous study reported migration defects of cortical neurons with shRNA-mediated knockdown of CRMP2. However, CRMP2 KI/KI mice, in which Cdk5-phosphorylation is inhibited, showed little defects in Purkinje cell migration and positioning. We hypothesized compensatory redundant functions of the other CRMPs, and analyzed the migration and positioning of Purkinje cells in the cerebellum in every combination of CRMP1 knockout (KO), CRMP2 KI/KI, and CRMP4 KO mice. Severe disturbance of migration and positioning of Purkinje cells were observed in the triple mutant mice. We also found motor coordination defects in the triple CRMPs mutant mice. These results suggest the importance of both, phosphorylation of CRMP2 by Cdk5 and the redundant functions of CRMP1 and CRMP4 in proper migration and positioning of Purkinje cells in developing cerebellum.
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影响因子：
4.3
作者：
Ohshima T
通讯作者：
Ohshima T
小脑皮质中的群落效应和浦肯野细胞迁移：扰码嵌合小鼠的分析
DOI：
10.1523/jneurosci.22-02-00464.2002
发表时间：
2002
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
Huaitao Yang;Patricia Jensen;D. Goldowitz
通讯作者：
D. Goldowitz
影响因子：
4.6
作者：
Tsutiya A;Nakano Y;Hansen-Kiss E;Kelly B;Nishihara M;Goshima Y;Corsmeier D;White P;Herman GE;Ohtani-Kaneko R
通讯作者：
Ohtani-Kaneko R
影响因子：
25
作者：
Ip, Jacque P. K.;Shi, Lei;Ip, Nancy Y.
通讯作者：
Ip, Nancy Y.
DOI：
10.1523/jneurosci.5563-11.2012
发表时间：
2012-01
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
N. Yamashita;T. Ohshima;F. Nakamura;Papachan Kolattukudy;J. Honnorat;K. Mikoshiba;Y. Goshima
通讯作者：
N. Yamashita;T. Ohshima;F. Nakamura;Papachan Kolattukudy;J. Honnorat;K. Mikoshiba;Y. Goshima