Activation of the Trk signaling pathway by extracellular zinc. Role of metalloproteinases |
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Authors: | Hwang Jung Jin Park Mi-Ha Choi So-Young Koh Jae-Young |
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Institution: | National Creative Research Initiative Center for the Study of CNS Zinc, Department of Neurology, University of Ulsan College of Medicine, Seoul 138-736, Korea. |
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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. |
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