脑源性神经营养因子通过调节γ-氨基丁酸A型（GABA(A)）受体的磷酸化、活性和细胞表面稳定性来调节快速突触抑制。
Brain-derived neurotrophic factor modulates fast synaptic inhibition by regulating GABA(A) receptor phosphorylation, activity, and cell-surface stability.
作者信息
Jovanovic Jasmina N, Thomas Philip, Kittler Josef T, Smart Trevor G, Moss Stephen J
机构信息
Department of Pharmacology, University College, London, WC1E 6BT, United Kingdom.
出版信息
J Neurosci. 2004 Jan 14;24(2):522-30. doi: 10.1523/JNEUROSCI.3606-03.2004.
Abstract
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 beta3-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.
摘要
γ-氨基丁酸能突触抑制的效能是控制神经元活动的一个主要因素。我们在此证明，脑源性神经营养因子在应用数分钟内就能调节γ-氨基丁酸A（GABA(A)）受体的活性，而GABA(A)受体是大脑中快速突触抑制的主要位点。从时间上看，这包括微小抑制性突触后电流（mIPSC）幅度的早期增强，随后是长时间的抑制。这种调节与蛋白激酶C（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激酶受体和PP2A根据受体β3亚基的磷酸化状态差异募集到GABA(A)受体上而促成的。因此，GABA(A)受体信号复合物的短暂形成有可能为GABA能突触可塑性基础上受体功能的急性变化提供一个基础。
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