Distinct dynein complexes defined by DYNLRB1 and DYNLRB2 regulate mitotic and male meiotic spindle bipolarity.

Distinct dynein complexes defined by DYNLRB1 and DYNLRB2 regulate mitotic and male meiotic spindle bipolarity.
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DynlRB1和DynLRB2定义的独特的动力蛋白复合物调节有丝分裂和男性减数分裂双极性。

DOI:
10.1038/s41467-023-37370-7
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发表时间:
2023-03-27
影响因子:
16.6
通讯作者:
Shibuya, Hiroki
Shibuya, Hiroki
中科院分区:
综合性期刊1区
文献类型:
--
作者:
He, Shuwen;Gillies, John P.;Zang, Juliana L.;Cordoba-Beldad, Carmen M.;Yamamoto, Io;Fujiwara, Yasuhiro;Grantham, Julie;DeSantis, Morgan E.;Shibuya, Hiroki

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纺锤体的形成依赖于典型的中心体系统,这是不同于无中心体卵母细胞减数分裂,但其具体的调控机制尚不清楚。在此,我们报告DYNLRB 2(动力蛋白轻链路障2型)是一个男性减数分裂上调动力蛋白轻链,是必不可少的纺锤体形成在减数分裂I。在Dynlrb 2 KO小鼠睾丸中,减数分裂进程在中期I被阻止,这是由于具有碎片化的中心粒周围物质(PCM)的多极纺锤体的形成。DYNLRB 2通过两种不同的途径抑制PCM片段化;抑制中心粒过早脱离并将NuMA(核有丝分裂器)靶向纺锤体极。广泛表达的有丝分裂对应物DYNLRB 1在有丝分裂细胞中具有相似的作用,并通过靶向NuMA和抑制中心粒过度复制来维持纺锤体双极性。我们的工作表明,含有DYNLRB 1或DYNLRB 2的两种不同的动力蛋白复合物分别用于有丝分裂和减数分裂纺锤体的形成,并且两者都以NuMA作为共同靶点。雄性减数分裂依赖于典型的中心体形成纺锤体,但这与无中心体卵母细胞减数分裂有何不同尚不清楚。在这里,他们表明精子中纺锤体的形成依赖于DYNLRB 2,类似于有丝分裂细胞中DYNLRB 1的活性。
Spindle formation in male meiosis relies on the canonical centrosome system, which is distinct from acentrosomal oocyte meiosis, but its specific regulatory mechanisms remain unknown. Herein, we report that DYNLRB2 (Dynein light chain roadblock-type-2) is a male meiosis-upregulated dynein light chain that is indispensable for spindle formation in meiosis I. In Dynlrb2 KO mouse testes, meiosis progression is arrested in metaphase I due to the formation of multipolar spindles with fragmented pericentriolar material (PCM). DYNLRB2 inhibits PCM fragmentation through two distinct pathways; suppressing premature centriole disengagement and targeting NuMA (nuclear mitotic apparatus) to spindle poles. The ubiquitously expressed mitotic counterpart, DYNLRB1, has similar roles in mitotic cells and maintains spindle bipolarity by targeting NuMA and suppressing centriole overduplication. Our work demonstrates that two distinct dynein complexes containing DYNLRB1 or DYNLRB2 are separately used in mitotic and meiotic spindle formations, respectively, and that both have NuMA as a common target. Male meiosis relies on canonical centrosomes for spindle formation, but how this differs from acentrosomal oocyte meiosis is unclear. Here they show that spindle formation in sperm relies on DYNLRB2, similar to the activity of DYNLRB1 in mitotic cells.
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