Department of Molecular, Cellular and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States
Jingjing Zhang
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden
Sharon R Garrott
Department of Molecular, Cellular and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States; Biological Chemistry, University of Michigan, Ann Arbor, United States
Department of Molecular, Cellular and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States; Biological Chemistry, University of Michigan, Ann Arbor, United States
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.
