Myosin X Interaction with KIF13B, a Crucial Pathway for Netrin-1-Induced Axonal Development.

Myosin X (Myo X) transports cargos to the tips of filopodia for cell adhesion, migration, and neuronal axon guidance. Deleted in Colorectal Cancer (DCC) is one of the Myo X cargos that is essential for Netrin-1-regulated axon pathfinding. The function of Myo X in axon development in vivo and the underlying mechanisms remain elusive. Here, we provide evidence for the role of Myo X in Netrin-1-DCC-regulated axon development in developing mouse neocortex. The knockout (KO) or knockdown (KD) of Myo X in cortical neurons of embryonic mouse brain impairs axon initiation and contralateral branching/targeting. Similar axon deficits are detected in Netrin-1-KO or DCC-KD cortical neurons. Further proteomic analysis of Myo X binding proteins identifies KIF13B (a kinesin family motor protein). The Myo X interaction with KIF13B is induced by Netrin-1. Netrin-1 promotes anterograde transportation of Myo X into axons in a KIF13B-dependent manner. KIF13B-KD cortical neurons exhibit similar axon deficits. Together, these results reveal Myo X-KIF13B as a critical pathway for Netrin-1-promoted axon initiation and branching/targeting.SIGNIFICANCE STATEMENT Netrin-1 increases Myosin X (Myo X) interaction with KIF13B, and thus promotes axonal delivery of Myo X and axon initiation and contralateral branching in developing cerebral neurons, revealing unrecognized functions and mechanisms underlying Netrin-1 regulation of axon development. Copyright © 2020 Yu et al.

Citation

Hua-Li Yu, Yun Peng, Yang Zhao, Yong-Sheng Lan, Bo Wang, Lu Zhao, Dong Sun, Jin-Xiu Pan, Zhao-Qi Dong, Lin Mei, Yu-Qiang Ding, Xiao-Juan Zhu, Wen-Cheng Xiong. Myosin X Interaction with KIF13B, a Crucial Pathway for Netrin-1-Induced Axonal Development. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2020 Nov 25;40(48):9169-9185

Mesh Tags

Substances

PMID: 33097641

search → result