title: LIM kinase 1 (LIMK1) interacts with tropomyosin-related kinase B (TrkB) and Mediates brain-derived neurotrophic factor (BDNF)-induced axonal elongation.
abstract: BDNF/TrkB signaling plays critical roles in axonal outgrowth of neurons, the process of which requires the remodeling of the cytoskeleton structure, including microtubules and filamentous actin. However, the mechanism by which BDNF/TrkB signaling regulates cytoskeleton reorganization is still unclear. Here, we identified a novel interaction between LIMK1 and TrkB, which is required for the BDNF-induced axonal elongation. We demonstrated that BDNF-induced TrkB dimerization led to LIMK1 dimerization and transphosphorylation independent of TrkB kinase activity, which could further enhance the activation and stabilization of LIMK1. Moreover, activated LIMK1 translocated to the membrane fraction and phosphorylated its substrate cofilin, thus promoting actin polymerization and axonal elongation. Our findings provided evidence of a novel mechanism for the BDNF-mediated signal transduction leading to axonal elongation.
authors.affiliation: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Dong
authors.forename: Yun-Song
authors.initials: YS
authors.lastname: Ji
authors.forename: Chang
authors.initials: C
authors.lastname: Cai
authors.forename: Zhe-Yu
authors.initials: ZY
authors.lastname: Chen
mesh_terms: D000818:Animals; D001369:Axons / Q000201:enzymology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D054461:Lim Kinases / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D055503:Protein Multimerization / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB; C515892:LIMK1 protein, human; D054461:Lim Kinases; C515894:Limk1 protein, rat