title: Zinc-mediated transactivation of TrkB potentiates the hippocampal mossy fiber-CA3 pyramid synapse.
abstract: The receptor tyrosine kinase, TrkB, is critical to diverse functions of the mammalian nervous system in health and disease. Evidence of TrkB activation during epileptogenesis in vivo despite genetic deletion of its prototypic neurotrophin ligands led us to hypothesize that a non-neurotrophin, the divalent cation zinc, can transactivate TrkB. We found that zinc activates TrkB through increasing Src family kinase activity by an activity-regulated mechanism independent of neurotrophins. One subcellular locale at which zinc activates TrkB is the postsynaptic density of excitatory synapses. Exogenous zinc potentiates the efficacy of the hippocampal mossy fiber (mf)-CA3 pyramid synapse by a TrkB-requiring mechanism. Long-term potentiation of this synapse is impaired by deletion of TrkB, inhibition of TrkB kinase activity, and by CaEDTA, a selective chelator of zinc. The activity-dependent activation of synaptic TrkB in a neurotrophin-independent manner provides a mechanism by which this receptor can regulate synaptic plasticity.
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Yang Z
authors.initials: YZ
authors.lastname: Huang
authors.forename: Enhui
authors.initials: E
authors.lastname: Pan
authors.forename: Zhi-Qi
authors.initials: ZQ
authors.lastname: Xiong
authors.forename: James O
authors.initials: JO
authors.lastname: McNamara
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D020813:Receptor, trkB / Q000096:biosynthesis* / Q000235:genetics; D013569:Synapses / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology*
chemical_list: D020813:Receptor, trkB; D015032:Zinc