PMID- 33097641 OWN - NLM STAT- MEDLINE DCOM- 20210216 LR - 20211204 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 40 IP - 48 DP - 2020 Nov 25 TI - Myosin X Interaction with KIF13B, a Crucial Pathway for Netrin-1-Induced Axonal Development. PG - 9169-9185 LID - 10.1523/JNEUROSCI.0929-20.2020 [doi] AB - 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. CI - Copyright (c) 2020 Yu et al. FAU - Yu, Hua-Li AU - Yu HL AD - Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106. AD - Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia 30912. AD - Institute of Cytology and Genetics, Northeast Normal University, Changchun 130024, People's Republic of China. FAU - Peng, Yun AU - Peng Y AD - Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia 30912. FAU - Zhao, Yang AU - Zhao Y AD - Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106. AD - Institute of Cytology and Genetics, Northeast Normal University, Changchun 130024, People's Republic of China. FAU - Lan, Yong-Sheng AU - Lan YS AD - Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106. AD - Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia 30912. FAU - Wang, Bo AU - Wang B AD - Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106. AD - Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia 30912. FAU - Zhao, Lu AU - Zhao L AD - Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106. AD - Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia 30912. AD - Institute of Cytology and Genetics, Northeast Normal University, Changchun 130024, People's Republic of China. FAU - Sun, Dong AU - Sun D AD - Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106. FAU - Pan, Jin-Xiu AU - Pan JX AD - Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106. FAU - Dong, Zhao-Qi AU - Dong ZQ AD - Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106. FAU - Mei, Lin AU - Mei L AD - Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106. AD - Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia 30912. FAU - Ding, Yu-Qiang AU - Ding YQ AD - Institute of Brain Sciences, Fudan University, Shanghai 200031, People's Republic of China. FAU - Zhu, Xiao-Juan AU - Zhu XJ AUID- ORCID: 0000-0001-8386-8064 AD - Institute of Cytology and Genetics, Northeast Normal University, Changchun 130024, People's Republic of China Wen-Cheng.Xiong@case.edu zhuxj720@nenu.edu.cn. FAU - Xiong, Wen-Cheng AU - Xiong WC AUID- ORCID: 0000-0001-9071-7598 AD - Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106 Wen-Cheng.Xiong@case.edu zhuxj720@nenu.edu.cn. AD - Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia 30912. LA - eng GR - R01 AG045781/AG/NIA NIH HHS/United States GR - RF1 AG045781/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20201023 PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (DCC Receptor) RN - 0 (Dcc protein, mouse) RN - 0 (Membrane Proteins) RN - 0 (Myo10 protein, mouse) RN - 0 (Ntn1 protein, mouse) RN - 158651-98-0 (Netrin-1) RN - EC 3.6.1.- (KIF13b protein, mouse) RN - EC 3.6.4.1 (Myosins) RN - EC 3.6.4.4 (Kinesins) SB - IM MH - Animals MH - Axons/*physiology MH - Cells, Cultured MH - Cerebral Cortex/cytology/growth & development MH - DCC Receptor/genetics/physiology MH - Female MH - Kinesins/genetics/*physiology MH - Male MH - Membrane Proteins/genetics/*physiology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Myosins/genetics/*physiology MH - Neocortex/cytology/growth & development MH - Netrin-1/genetics/*physiology MH - Pregnancy PMC - PMC7687062 OTO - NOTNLM OT - KIF13B OT - Myo X OT - Netrin-1 OT - axon OT - axon branching OT - axon initiation EDAT- 2020/10/25 06:00 MHDA- 2021/02/17 06:00 PMCR- 2020/11/25 CRDT- 2020/10/24 05:29 PHST- 2020/04/23 00:00 [received] PHST- 2020/09/04 00:00 [revised] PHST- 2020/10/17 00:00 [accepted] PHST- 2020/10/25 06:00 [pubmed] PHST- 2021/02/17 06:00 [medline] PHST- 2020/10/24 05:29 [entrez] PHST- 2020/11/25 00:00 [pmc-release] AID - JNEUROSCI.0929-20.2020 [pii] AID - JN-RM-0929-20 [pii] AID - 10.1523/JNEUROSCI.0929-20.2020 [doi] PST - ppublish SO - J Neurosci. 2020 Nov 25;40(48):9169-9185. doi: 10.1523/JNEUROSCI.0929-20.2020. Epub 2020 Oct 23.