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

Nature Communications · 9 authors, 3 centres

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TL;DR

This study used knockout mice and knockdown cell lines to show that two different dynein light chains, DYNLRB1 and DYNLRB2, form distinct complexes that are crucial for maintaining spindle bipolarity during mitosis and male meiosis, respectively, by targeting the protein NuMA.

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The researchers investigated the roles of dynein light chains DYNLRB1 and DYNLRB2 in spindle formation. Using Dynlrb2 knockout mice, they found that loss of DYNLRB2 arrests male meiosis in metaphase I due to multipolar spindles, caused by premature centriole disengagement and mislocalization of NuMA. DYNLRB2 inhibits these defects by suppressing premature centriole disengagement and targeting NuMA to spindle poles. The study also showed that the ubiquitously expressed DYNLRB1 performs a similar role in mitotic cells by targeting NuMA and suppressing centriole overduplication. The results demonstrate that distinct dynein complexes containing DYNLRB1 or DYNLRB2 are separately utilized in mitotic and meiotic spindle formation, with NuMA as a common target.

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other

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preclinical research

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ORIGINAL PAPER

PMC10042829

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

Nature Communications

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ABSTRACT

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.

CITATION EXPORT

Shuwen He, John P. Gillies, Juliana L. Zang et al.. Distinct dynein complexes defined by DYNLRB1 and DYNLRB2 regulate mitotic and male meiotic spindle bipolarity. Nature Communications. (2023). https://doi.org/10.1038/s41467-023-37370-7

AUTHORS

9 · 3 CENTRES

Shuwen He, John P. Gillies, Juliana L. Zang, Carmen M. Córdoba-Beldad, Io Yamamoto, Yasuhiro Fujiwara, Julie Grantham, Morgan E. DeSantis, Hiroki Shibuya

1grid.8761.80000 0000 9919 9582Department of Chemistry and Molecular Biology, University of Gothenburg, SE-41390 Gothenburg, Sweden
2grid.214458.e0000000086837370Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109 USA
3grid.26999.3d0000 0001 2151 536XInstitute for Quantitative Biosciences, University of Tokyo, 1-1-1 Yayoi, Tokyo, 113-0032 Japan