Radmis, a novel mitotic spindle protein that functions in cell division of neural progenitors.
Radmis, a novel mitotic spindle protein that functions in cell division of neural progenitors.
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DOI：
10.1371/journal.pone.0079895
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sakakibara S
中科院分区：
文献类型：
--
作者：
Yumoto T;Nakadate K;Nakamura Y;Sugitani Y;Sugitani-Yoshida R;Ueda S;Sakakibara S
神经干/祖细胞（NSPCs）的发育动力学对胚胎和成体神经发生至关重要，但其调控因素尚未完全了解。通过差异消减筛选与NSPCs与其分化的后代，我们确定了radmis（径向纤维和有丝分裂纺锤体）/ckap 2l基因，一种新的微管相关蛋白（MAP）富集在NSPCs。Radmis是E3-泛素连接酶、后期促进复合物/细胞周期体（APC/C）的推定底物，并且通过KEN盒降解。Radmis在整个生命过程中活跃的神经发生区域高度表达，其分布在NSPC分裂过程中受到动态调节。在胚胎和围产期脑中，神经根定位于分裂的NSPCs的双极有丝分裂纺锤体和放射状纤维（基底突起）。随着中枢神经系统发育的进行，除了几个神经源性区域外，大多数脑区域中的radmis表达丢失。在成人脑中，radmis表达持续存在于缓慢分裂的干细胞和快速扩增的祖细胞的有丝分裂纺锤体中。在体外过表达radmis诱导微管的超稳定，有丝分裂纺锤体形成的严重缺陷，和有丝分裂停滞。在体内获得的功能，在子宫内电穿孔显示，radmis指导减少NSPC增殖和伴随的增加细胞周期退出，导致减少Tbr 2阳性的基础祖细胞群体和收缩的胚胎脑室下区。此外，由于shRNAs的作用，胚根功能丧失，导致有丝分裂形成多极纺锤体结构，并伴随着染色体分离的灾难，包括两个分离的子核之间的长染色体桥。这些发现揭示了radmis在NSPCs有丝分裂纺锤体形成和细胞周期进展中不可或缺的作用。
Developmental dynamics of neural stem/progenitor cells (NSPCs) are crucial for embryonic and adult neurogenesis, but its regulatory factors are not fully understood. By differential subtractive screening with NSPCs versus their differentiated progenies, we identified the radmis (radial fiber and mitotic spindle)/ckap2l gene, a novel microtubule-associated protein (MAP) enriched in NSPCs. Radmis is a putative substrate for the E3-ubiquitin ligase, anaphase promoting complex/cyclosome (APC/C), and is degraded via the KEN box. Radmis was highly expressed in regions of active neurogenesis throughout life, and its distribution was dynamically regulated during NSPC division. In embryonic and perinatal brains, radmis localized to bipolar mitotic spindles and radial fibers (basal processes) of dividing NSPCs. As central nervous system development proceeded, radmis expression was lost in most brain regions, except for several neurogenic regions. In adult brain, radmis expression persisted in the mitotic spindles of both slowly-dividing stem cells and rapid amplifying progenitors. Overexpression of radmis in vitro induced hyper-stabilization of microtubules, severe defects in mitotic spindle formation, and mitotic arrest. In vivo gain-of-function using in utero electroporation revealed that radmis directed a reduction in NSPC proliferation and a concomitant increase in cell cycle exit, causing a reduction in the Tbr2-positive basal progenitor population and shrinkage of the embryonic subventricular zone. Besides, radmis loss-of-function by shRNAs induced the multipolar mitotic spindle structure, accompanied with the catastrophe of chromosome segregation including the long chromosome bridge between two separating daughter nuclei. These findings uncover the indispensable role of radmis in mitotic spindle formation and cell-cycle progression of NSPCs.
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影响因子：
5.3
作者：
Hong, Kyung Uk;Park, Young Soo;Park, Joobae
通讯作者：
Park, Joobae
DOI：
10.1523/jneurosci.4185-12.2013
发表时间：
2013-02-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Hodge RD;Garcia AJ 3rd;Elsen GE;Nelson BR;Mussar KE;Reiner SL;Ramirez JM;Hevner RF
通讯作者：
Hevner RF
影响因子：
13.9
作者：
Kriegstein A;Alvarez-Buylla A
通讯作者：
Alvarez-Buylla A
影响因子：
2.5
作者：
ALTMAN, J;ANDERSON, WJ
通讯作者：
ANDERSON, WJ
影响因子：
25
作者：
Denise, A;Garcia, R;Sofroniew, MV
通讯作者：
Sofroniew, MV