Myosin X Interaction with KIF13B, a Crucial Pathway for Netrin-1-Induced Axonal Development
- Hua-Li Yu1,2,3,*,
- Yun Peng2,*,
- Yang Zhao1,3,
- Yong-Sheng Lan1,2,
- Bo Wang1,2,
- Lu Zhao1,2,3,
- Dong Sun1,
- Jin-Xiu Pan1,
- Zhao-Qi Dong1,
- Lin Mei1,2,
- Yu-Qiang Ding4,
- Xiao-Juan Zhu3, and
- Wen-Cheng Xiong1,2
- 1Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106
- 2Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia 30912
- 3Institute of Cytology and Genetics, Northeast Normal University, Changchun 130024, People's Republic of China
- 4Institute of Brain Sciences, Fudan University, Shanghai 200031, People's Republic of China
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Author contributions: L.M. and W.-C.X. designed research; H.L.-Y., Y.P., Y.Z., Y.-S.L., B.W., L.Z., D.S., J.-X.P., and Z.-Q.D. performed research; Y.-Q.D. and X.-J.Z. contributed unpublished reagents/analytic tools; H.L.-Y. and Y.P. analyzed data; H.L.-Y. wrote the paper.
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↵*H.L.-Y. and Y.P. have contributed equally to this work.
Abstract
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.
- Received April 23, 2020.
- Revision received September 4, 2020.
- Accepted October 17, 2020.
- Copyright © 2020 Yu et al.
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