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Publication : The KASH5 protein involved in meiotic chromosomal movements is a novel dynein activating adaptor.

First Author  Agrawal R Year  2022
Journal  Elife Volume  11
PubMed ID  35703493 Mgi Jnum  J:326432
Mgi Id  MGI:7295027 Doi  10.7554/eLife.78201
Citation  Agrawal R, et al. (2022) The KASH5 protein involved in meiotic chromosomal movements is a novel dynein activating adaptor. Elife 11:e78201
abstractText  Dynein harnesses ATP hydrolysis to move cargo on microtubules in multiple biological contexts. Dynein meets a unique challenge in meiosis by moving chromosomes tethered to the nuclear envelope to facilitate homolog pairing essential for gametogenesis. Though processive dynein motility requires binding to an activating adaptor, the identity of the activating adaptor required for dynein to move meiotic chromosomes is unknown. We show that the meiosis-specific nuclear-envelope protein KASH5 is a dynein activating adaptor: KASH5 directly binds dynein using a mechanism conserved among activating adaptors and converts dynein into a processive motor. We map the dynein-binding surface of KASH5, identifying mutations that abrogate dynein binding in vitro and disrupt recruitment of the dynein machinery to the nuclear envelope in cultured cells and mouse spermatocytes in vivo. Our study identifies KASH5 as the first transmembrane dynein activating adaptor and provides molecular insights into how it activates dynein during meiosis.
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