Activation of the Trk signaling pathway by extracellular zinc. Role of metalloproteinases.
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.
Hwang
Jung Jin
JJ
National Creative Research Initiative Center for the Study of CNS Zinc, Department of Neurology, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Park
Mi-Ha
MH
Choi
So-Young
SY
Koh
Jae-Young
JY
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*
D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB; D045726:Metalloproteases; D015032:Zinc