title: JIP3 mediates TrkB axonal anterograde transport and enhances BDNF signaling by directly bridging TrkB with kinesin-1.
abstract: Brain-derived neurotrophic factor (BDNF), secreted from target tissues, binds and activates TrkB receptors, located on axonal terminals of the innervating neurons, and thereby initiates retrograde signaling. Long-range anterograde transport of TrkB in axons and dendrites requires kinesin-mediated transport. However, it remains unknown whether anterograde TrkB transport mechanisms are the same in axons versus in dendrites. Here, we show that c-Jun NH(2)-terminal kinase-interacting protein 3 (JIP3) binds directly to TrkB, via a minimal 12 aa domain in the TrkB juxtamembrane region, and links TrkB to kinesin-1. The JIP3/TrkB interaction selectively drives TrkB anterograde transport in axons but not in dendrites of rat hippocampal neurons. Moreover, we find that TrkB axonal transport mediated by JIP3 could regulate BDNF-induced Erk activation and axonal filopodia formation. Our findings demonstrate a role for JIP3-mediated TrkB anterograde axonal transport in recruiting more TrkB into distal axons and facilitating BDNF-induced retrograde signaling and synapse modulation, which provides a novel mechanism of how the TrkB anterograde transport can be coupled to BDNF signaling in distal axons.
authors.affiliation: Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Shandong University, Jinan, Shandong 250012, People's Republic of China.
authors.forename: Shu-Hong
authors.initials: SH
authors.lastname: Huang
authors.forename: Shan
authors.initials: S
authors.lastname: Duan
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.forename: Zhao
authors.initials: Z
authors.lastname: Geng
authors.forename: Jing
authors.initials: J
authors.lastname: Yan
authors.forename: Hai-Ji
authors.initials: HJ
authors.lastname: Sun
authors.forename: Zhe-Yu
authors.initials: ZY
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002461:Cell Line, Transformed; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D016547:Kinesins; D008026:Ligation / Q000379:methods; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D011554:Pseudopodia / Q000187:drug effects / Q000502:physiology; D051381:Rats; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000235:genetics; D012584:Sciatic Nerve / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019208:Brain-Derived Neurotrophic Factor; D008164:Luminescent Proteins; C485750:MAPK8IP3 protein, human; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D018123:Receptors, Interleukin; D020813:Receptor, trkB; D016547:Kinesins