Department of Chemistry and Molecular Biology, University of Gothenburg, SE-41390, Gothenburg, Sweden.
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
Nat Commun. 2023 Mar 27;14(1):1715. doi: 10.1038/s41467-023-37370-7.
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.
在雄性减数分裂中,纺锤体的形成依赖于经典的中心体系统,这与无中心体的卵母细胞减数分裂不同,但具体的调控机制尚不清楚。本文报道了 DYNLRB2(动力蛋白轻链阻遏型-2)是一种雄性减数分裂上调的动力蛋白轻链,对于减数分裂 I 中纺锤体的形成是必不可少的。在 Dynlrb2 KO 小鼠睾丸中,由于形成具有碎片化中心粒周围物质(PCM)的多极纺锤体,减数分裂进程停滞在中期 I。DYNLRB2 通过两种不同的途径抑制 PCM 碎片化;抑制过早的中心粒脱离和将 NuMA(核有丝分裂装置)靶向纺锤体极。广泛表达的有丝分裂对应物 DYNLRB1 在有丝分裂细胞中具有相似的作用,通过靶向 NuMA 和抑制中心粒过度复制来维持纺锤体的两极。我们的工作表明,两种含有 DYNLRB1 或 DYNLRB2 的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,并且都有 NuMA 作为共同的靶标。