Coexpressed Auxiliary Subunits Exhibit Distinct Modulatory Profiles on AMPA Receptor Function

Coexpressed Auxiliary Subunits Exhibit Distinct Modulatory Profiles on AMPA Receptor Function
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DOI:
10.1016/j.neuron.2014.07.004
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发表时间:
2014-08-06
期刊:
影响因子:
16.2
通讯作者:
von Engelhardt, Jakob
von Engelhardt, Jakob
中科院分区:
医学1区
文献类型:
--
作者:
Khodosevich, Konstantin;Jacobi, Eric;von Engelhardt, Jakob

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AMPA受体的门控特性和表面转运受辅助亚单位的调节。在这里,我们研究了属于两个不同类别的共表达辅助亚基的功能。我们重点研究了TARP-8和CKAMP44在齿状回颗粒细胞中的表达,因为这两个亚基在齿状回颗粒细胞中都有高表达。TARP-8和CKAMP44可降低突触的失活率,但对受体失敏有相反的影响,这是它们对突触短期可塑性的差异性调制的原因。此外,长期可塑性(LTP)需要TARP Gamma-8,但不需要CKAMP44。这两个辅助亚基的共同表达是AMPARs有效靶向DG颗粒细胞表面所必需的。最后,电生理和生化证据支持CKAMP44和TARP-8可以包含在同一AMPAR复合体中的观点。
Gating properties and surface trafficking of AMPA receptors (AMPARs) are modulated by auxiliary sub-units. Here we studied the function of coexpressed auxiliary subunits belonging to two different classes. We focused on TARP gamma-8 and CKAMP44 in dentate gyrus (DG) granule cells, since both subunits are highly expressed in this cell type. TARP gamma-8 and CKAMP44 decrease the rate of deactivation but have an opposing influence on receptor desensitization, which accounts for their differential modulation of synaptic short-term plasticity. Furthermore, long-term plasticity (LTP) requires TARP gamma-8 but not CKAMP44. The coexpression of both auxiliary subunits is necessary for the efficient targeting of AMPARs to the cell surface of DG granule cells. Finally, electrophysiological and biochemical evidence support the notion that CKAMP44 and TARP gamma-8 can be contained in the same AMPAR complex.