title: c-Jun NH2-terminal kinase (JNK)-interacting protein-3 (JIP3) regulates neuronal axon elongation in a kinesin- and JNK-dependent manner.
abstract: The development of neuronal polarity is essential for the establishment of the accurate patterning of neuronal circuits in the brain. However, little is known about the underlying molecular mechanisms that control rapid axon elongation during neuronal development. Here, we report that c-Jun NH2-terminal kinase (JNK)-interacting protein-3 (JIP3) is highly expressed at axon tips during the critical period for axon development. Using gain- and loss-of-function approaches, immunofluorescence analysis, and in utero electroporation, we find that JIP3 can enhance axon elongation in primary hippocampal neurons and cortical neurons in vivo. We further demonstrate that JIP3 promotes axon elongation in a kinesin- and JNK-dependent manner using several deletion mutants of JIP3. Next, we demonstrate that the successful transportation of JIP3 to axon tips by kinesin is a prerequisite for enhancing JNK phosphorylation in this area and therefore promotes axon elongation, constituting a novel mechanism for coupling JIP3 anterograde transport with JNK signaling at the distal axons and axon elongation. Finally, our immunofluorescence data suggest that the activation of JNK at axon tips facilitates axon elongation by modulating cofilin activity and actin filament dynamics. These findings may have important implications for our understanding of neuronal axon elongation during development.
authors.affiliation: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, No. 4 Wenhua Xi Road, Jinan, Shandong 250012.
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, No. 4 Wenhua Xi Road, Jinan, Shandong 250012.
authors.forename: Nuo
authors.initials: N
authors.lastname: Yu
authors.affiliation: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, No. 4 Wenhua Xi Road, Jinan, Shandong 250012.
authors.forename: Lu-Kai
authors.initials: LK
authors.lastname: Zhai
authors.affiliation: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, No. 4 Wenhua Xi Road, Jinan, Shandong 250012.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, No. 4 Wenhua Xi Road, Jinan, Shandong 250012.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Xing-Yu
authors.initials: XY
authors.lastname: Jiang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, No. 4 Wenhua Xi Road, Jinan, Shandong 250012. Electronic address: zheyuchen@sdu.edu.cn.
authors.forename: Zhe-Yu
authors.initials: ZY
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000196:embryology; D051338:Cofilin 1 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D044085:Microfluidics; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C495811:Cfl1 protein, mouse; C495812:Cfl1 protein, rat; D051338:Cofilin 1; C403619:Mapk8ip3 protein, mouse; D009419:Nerve Tissue Proteins; C554781:mapk8ip3 protein, rat; D016547:Kinesins
keywords: Axon; Axon Elongation; Cofilin; JIP3; Jun NH2-terminal Kinase (JNK); Kinesin; Neurons