This study identifies Nesprin-2 as a bidirectional motor adaptor during nuclear migration in developing neurons. Nesprin-2 coordinates dynein complex and kinesin-1 and activates prolonged bidirectional movements of the nucleus along forward moving microtubules in migrating neurons.
See details in Zhou, et. al. (2024) J Cell Biol.
Chuying Zhou, You Kure Wu, Fumiyoshi Ishidate, Takahiro K Fujiwara, Mineko Kengaku (2024) Nesprin-2 coordinates opposing microtubule motors during nuclear migration in neurons., The Journal of cell biology, Volume 223, Number 11
Published in 2024 Nov 4 (Electronic publication in Aug. 8, 2024, midnight )
(Abstract) Nuclear migration is critical for the proper positioning of neurons in the developing brain. It is known that bidirectional microtubule motors are required for nuclear transport, yet the mechanism of the coordination of opposing motors is still under debate. Using mouse cerebellar granule cells, we demonstrate that Nesprin-2 serves as a nucleus-motor adaptor, coordinating the interplay of kinesin-1 and dynein. Nesprin-2 recruits dynein-dynactin-BicD2 independently of the nearby kinesin-binding LEWD motif. Both motor binding sites are required to rescue nuclear migration defects caused by the loss of function of Nesprin-2. In an intracellular cargo transport assay, the Nesprin-2 fragment encompassing the motor binding sites generates persistent movements toward both microtubule minus and plus ends. Nesprin-2 drives bidirectional cargo movements over a prolonged period along perinuclear microtubules, which advance during the migration of neurons. We propose that Nesprin-2 keeps the nucleus mobile by coordinating opposing motors, enabling continuous nuclear transport along advancing microtubules in migrating cells.(MeSH Terms)