title: Activation of the Trk signaling pathway by extracellular zinc. Role of metalloproteinases.
abstract: In certain brain regions, extracellular zinc concentrations can rise precipitously as intense neuronal activity releases large amounts of zinc from the nerve terminals. Although zinc release has been suggested to play a pathological role, its precise physiological effect is poorly understood. Here, we report that exposure to micromolar quantities of zinc for only a few minutes robustly and specifically activated tropomyosin-related kinase (Trk) receptors, most likely TrkB, in cultured cortical neurons. We further found that Trk activation by zinc is extracellularly mediated by activation of metalloproteinases, which release pro-BDNF from cells and convert pro-BDNF to mature BDNF. These results suggest that activity-dependent release of extracellular zinc leads to metalloproteinase activation, which plays a critically important role in Trk receptor activation at zinc-containing synapses.
authors.affiliation: National Creative Research Initiative Center for the Study of CNS Zinc, Department of Neurology, University of Ulsan College of Medicine, Seoul 138-736, Korea.
authors.forename: Jung Jin
authors.initials: JJ
authors.lastname: Hwang
authors.forename: Mi-Ha
authors.initials: MH
authors.lastname: Park
authors.forename: So-Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Koh
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D045726:Metalloproteases / Q000502:physiology*; D051379:Mice; D009473:Neuronal Plasticity; D010766:Phosphorylation; D020813:Receptor, trkB / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D015032:Zinc / Q000494:pharmacology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB; D045726:Metalloproteases; D015032:Zinc