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

Shuwen He, John P. Gillies, Juliana L. Zang, Carmen M. Córdoba-Beldad, Io Yamamoto, Yasuhiro Fujiwara, Julie Grantham, Morgan E. DeSantis and Hiroki Shibuya ()
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Shuwen He: University of Gothenburg
John P. Gillies: University of Michigan
Juliana L. Zang: University of Michigan
Carmen M. Córdoba-Beldad: University of Gothenburg
Io Yamamoto: University of Gothenburg
Yasuhiro Fujiwara: University of Tokyo
Julie Grantham: University of Gothenburg
Morgan E. DeSantis: University of Michigan
Hiroki Shibuya: University of Gothenburg

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-37370-7

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