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

• Published in: Nature communications Vol. 14; no. 1; pp. 1715 - 15
• Main Authors: He, Shuwen, Gillies, John P., Zang, Juliana L., Córdoba-Beldad, Carmen M., Yamamoto, Io, Fujiwara, Yasuhiro, Grantham, Julie, DeSantis, Morgan E., Shibuya, Hiroki
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.03.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 14/63; 38/1; 38/77; 38/89; 631/136/2434/1822; 631/80/128/1441; 631/80/641/1633; 64/60; 82/111; Animals; Biologi; Biological Sciences; Bipolarity; Cell Biology; Cellbiologi; Centrosome - metabolism; Centrosomes; Chains; Dynein; Dyneins - genetics; Dyneins - metabolism; Gametocytes; Humanities and Social Sciences; Male; Males; Meiosis; Metaphase; Mice; multidisciplinary; Regulatory mechanisms (biology); Science; Science (multidisciplinary); Spindle Apparatus - metabolism; Spindles; Yeast
• ISSN: 2041-1723; 2041-1723
• 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. 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.