JIP1 mediates anterograde transport of Rab10 cargos during neuronal polarization.
Axon development and elongation require strictly controlled new membrane addition. Previously, we have shown the involvement of Rab10 in directional membrane insertion of plasmalemmal precursor vesicles (PPVs) during neuronal polarization and axonal growth. However, the mechanism responsible for PPV transportation remains unclear. Here we show that c-Jun N-terminal kinase-interacting protein 1 (JIP1) interacts with GTP-locked active form of Rab10 and directly connects Rab10 to kinesin-1 light chain (KLC). The kinesin-1/JIP1/Rab10 complex is required for anterograde transport of PPVs during axonal growth. Downregulation of JIP1 or KLC or disrupting the formation of this complex reduces anterograde transport of PPVs in developing axons and causes neuronal polarity defect. Furthermore, this complex plays an important role in neocortical neuronal polarization of rats in vivo. Thus, this study has demonstrated a mechanism underlying directional membrane trafficking involved in axon development.
Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, and School of Life Sciences, Shanghai University, Shanghai 200444, China.
Cai-Yun
CY
Deng
Wen-Liang
WL
Lei
Xiao-Hui
XH
Xu
Xiang-Chun
XC
Ju
Yang
Y
Liu
Zhen-Ge
ZG
Luo
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000166:cytology; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D022082:Cellular Structures / Q000378:metabolism; D004622:Embryo, Mammalian; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D016547:Kinesins; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020825:T-Box Domain Proteins / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D019394:Ki-67 Antigen; D008164:Luminescent Proteins; C110528:Mapk8ip1 protein, rat; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; C082378:Rab10 protein, rat; D020825:T-Box Domain Proteins; D016547:Kinesins; D020691:rab GTP-Binding Proteins
Jip1; Rab10; neuronal polarity; vesicle trafficking