Zinc-mediated transactivation of TrkB potentiates the hippocampal mossy Fiber-CA3 pyramid synapse
Zinc-mediated transactivation of TrkB potentiates the hippocampal mossy Fiber-CA3 pyramid synapse
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DOI：
10.1016/j.neuron.2007.11.026
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发表时间：
2008-02-28
期刊：
影响因子：
16.2
通讯作者：
McNamara, James O.
中科院分区：
文献类型：
--
作者：
Huang, Yang Z.;Pan, Enhui;McNamara, James O.
受体酪氨酸激酶TrkB对哺乳动物神经系统在健康和疾病中的多种功能至关重要。尽管其原型神经营养因子配体的基因缺失，但在体内癫痫发生期间TrkB激活的证据使我们假设非神经营养因子，二价阳离子锌，可以反式激活TrkB。我们发现，锌激活TrkB通过增加Src家族激酶活性的活性调节机制独立的神经营养因子。锌激活TrkB的一个亚细胞区域是兴奋性突触的突触后密度。外源性锌通过TrkB需要机制增强海马苔藓纤维（mf）-CA 3锥体突触的功效。该突触的长时程增强通过TrkB的缺失、TrkB激酶活性的抑制和CaEDTA（锌的选择性螯合剂）而受损。突触TrkB以神经营养因子非依赖性方式的活性依赖性激活提供了该受体可以调节突触可塑性的机制。
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. Longterm 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.