title: GIT1 enhances neurite outgrowth by stimulating microtubule assembly.
abstract: GIT1, a G-protein-coupled receptor kinase interacting protein, has been reported to be involved in neurite outgrowth. However, the neurobiological functions of the protein remain unclear. In this study, we found that GIT1 was highly expressed in the nervous system, and its expression was maintained throughout all stages of neuritogenesis in the brain. In primary cultured mouse hippocampal neurons from GIT1 knockout mice, there was a significant reduction in total neurite length per neuron, as well as in the average length of axon-like structures, which could not be prevented by nerve growth factor treatment. Overexpression of GIT1 significantly promoted axon growth and fully rescued the axon outgrowth defect in the primary hippocampal neuron cultures from GIT1 knockout mice. The GIT1 N terminal region, including the ADP ribosylation factor-GTPase activating protein domain, the ankyrin domains and the Spa2 homology domain, were sufficient to enhance axonal extension. Importantly, GIT1 bound to many tubulin proteins and microtubule-associated proteins, and it accelerated microtubule assembly in vitro. Collectively, our findings suggest that GIT1 promotes neurite outgrowth, at least partially by stimulating microtubule assembly. This study provides new insight into the cellular and molecular pathogenesis of GIT1-associated neurological diseases.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Stem Cell Research Center, Ren Ji Hospital, School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yi-Sheng
authors.initials: YS
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Stem Cell Research Center, Ren Ji Hospital, School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Stem Cell Research Center, Ren Ji Hospital, School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Stem Cell Research Center, Ren Ji Hospital, School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Wei-Liang
authors.initials: WL
authors.lastname: Xia
authors.affiliation: Department of Neurology, Shanghai Renji Hospital, Shanghai, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Stem Cell Research Center, Ren Ji Hospital, School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Hai-Lian
authors.identifier: 0000-0002-1419-4876
authors.initials: HL
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Stem Cell Research Center, Ren Ji Hospital, School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China; Collarative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Wei-Qiang
authors.identifier: 0000-0003-3742-6665
authors.initials: WQ
authors.lastname: Gao
keywords: GIT1; hippocampal neurons; microtubule-associated proteins; nerve regeneration; neural regeneration; neurite outgrowth; tubulin