Brain-derived neurotrophic factor modulates fast synaptic inhibition by regulating GABAA receptor phosphorylation, activity, and cell-surface stability
Brain-derived neurotrophic factor modulates fast synaptic inhibition by regulating GABAA receptor phosphorylation, activity, and cell-surface stability
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DOI：
10.1523/jneurosci.3606-03.2004
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发表时间：
2004-01-14
影响因子：
5.3
通讯作者：
Moss, SJ
中科院分区：
文献类型：
--
作者：
Jovanovic, JN;Thomas, P;Moss, SJ
GABA能突触抑制的功效是控制神经元活动的主要因素。我们在这里证明，脑源性神经营养因子调节GABA（A）受体的活性，快速突触抑制在大脑中的主要网站，在应用分钟。在时间上，这包括微型IPSC振幅的早期增强，随后是长时间的抑制。这种调节与PKC介导的磷酸化增强同时发生，随后是蛋白磷酸酶2A（PP2A）介导的GABA（A）受体去磷酸化。从机制上讲，这些事件是由PKC（活化C激酶的受体）和PP2A对GABA（A）受体的差异募集促进的，这取决于受体β（3）亚基的磷酸化状态。因此，GABA（A）受体信号复合物的瞬时形成有可能为GABA能突触可塑性的受体功能的急性变化提供基础。
The efficacy of GABAergic synaptic inhibition is a principal factor in controlling neuronal activity. We demonstrate here that brain-derived neurotrophic factor modulates the activity of GABA(A) receptors, the main sites of fast synaptic inhibition in the brain, within minutes of application. Temporally, this comprised an early enhancement in the miniature IPSC amplitude, followed by a prolonged depression. This modulation was concurrent with enhanced PKC-mediated phosphorylation, followed by protein phosphatase 2A (PP2A)-mediated dephosphorylation of the GABA(A) receptor. Mechanistically, these events were facilitated by differential recruitment of PKC, receptor for activated C-kinase, and PP2A to GABA(A) receptors, depending on the phosphorylation state of the receptor beta(3)-subunit. Thus, transient formation of GABA(A) receptor signaling complexes has the potential to provide a basis for acute changes in receptor function underlying GABAergic synaptic plasticity.