Constitutive tyrosine phosphorylation of the GABA(A) receptor gamma 2 subunit in rat brain.
Constitutive tyrosine phosphorylation of the GABA(A) receptor gamma 2 subunit in rat brain.
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发表时间：
2001
影响因子：
4.7
通讯作者：
N. Brandon;P. Delmas;J. Hill;T. Smart;S. Moss
中科院分区：
文献类型：
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作者：
N. Brandon;P. Delmas;J. Hill;T. Smart;S. Moss
GABA(A) 受体是大脑中快速突触抑制的主要部位，主要由 α、β 和 γ2 亚基组成。根据重组受体的研究，γ2 亚基胞内结构域内残基 365 和 367 (Y365/367) 的直接酪氨酸磷酸化在调节 GABA(A) 受体功能中发挥着重要作用。为了解决这些观察结果与神经元 GABA(A) 受体的相关性，我们研究了大脑中 γ2 亚基的磷酸化。在成年大鼠大脑中，γ2 亚基在酪氨酸残基上被磷酸化，包括使用磷酸特异性抗血清定义的 Y365/367。在培养的皮质神经元中，Y365/367 的磷酸化受到高度调节，并且仅在抑制酪氨酸磷酸酶时才明显。我们还确定酪氨酸激酶 Src 能够与受体 β 和 γ2 亚基的细胞内结构域特异性相互作用。这可能将酪氨酸激酶活性特异性定位于 GABA(A) 受体，促进激酶激活后受体酪氨酸快速磷酸化。我们的结果表明，γ2 亚基的酪氨酸磷酸化（可能是通过密切相关的 Src）可能是调节大脑中 GABA(A) 受体功能的动态机制。
GABA(A) receptors are the major sites of fast synaptic inhibition in the brain, where they are predominantly composed of alpha, beta and gamma2 subunits. A role for direct tyrosine phosphorylation of residues 365 and 367 (Y365/367) within the intracellular domain of the gamma2 subunit has been suggested to be important in modulating GABA(A) receptor function, based on the study of recombinant receptors. To address the relevance of these observations for neuronal GABA(A) receptors we have studied the phosphorylation of the gamma2 subunit in the brain. In adult rat brain the gamma2 subunit is phosphorylated on tyrosine residues, including Y365/367 as defined using a phosphospecific antisera. In cultured cortical neurones, phosphorylation of Y365/367 is highly regulated and was only evident upon inhibition of tyrosine phosphatases. We also establish that the tyrosine kinase Src is capable of specifically interacting with the intracellular domains of receptor beta and gamma2 subunits. This may specifically localise tyrosine kinase activity to GABA(A) receptors, facilitating rapid receptor tyrosine phosphorylation upon kinase activation. Together our results suggests that tyrosine phosphorylation of the gamma2 subunit, possibly by closely associated Src, may be a dynamic mechanism for regulating GABA(A) receptor function in the brain.