Climbing fiber-evoked Purkinje cell discharge reduces expression of GABA(A) receptor-associated protein and decreases its interaction with GABA(A) receptors.
Climbing fiber-evoked Purkinje cell discharge reduces expression of GABA(A) receptor-associated protein and decreases its interaction with GABA(A) receptors.
复制标题
DOI：
10.1111/j.1471-4159.2010.07119.x
复制
发表时间：
2011-04
影响因子：
4.7
通讯作者：
Barmack NH
中科院分区：
文献类型：
--
作者：
Qian Z;Yakhnitsa V;Barmack NH
持续的神经元活动部分通过改变基因表达来诱导突触重塑。我们使用小脑浦肯野细胞上的主要攀爬纤维途径来研究持续攀爬纤维诱发的谷氨酸突触传递对与抑制性 GABAa 受体功能调节相关的蛋白质的转录、表达和磷酸化的影响。双目水平视动刺激用于调节兔子和小鼠絮状和结节中浦肯野细胞的攀爬纤维信号。在后→前方向刺激的眼睛同侧的绒球和结节中的浦肯野细胞接收到增加的攀爬纤维活性。在前→后方向刺激的眼睛同侧的绒球和结节中的浦肯野细胞接收到的攀爬纤维活性降低。我们利用差异显示 RT-PCR 技术鉴定了絮状和结节性浦肯野细胞中基因转录物水平的变化。攀爬纤维输入的增加降低了 GABA 受体相关蛋白 (GABARAP) 的转录水平和表达。使用蛋白质“下拉”技术，我们发现 GABARAP 与丝氨酸磷酸化 GABAaγ2、gephyrin 和 β-微管蛋白相互作用。 GABAaγ2 的丝氨酸去磷酸化降低了 GABARAP 与 GABAaγ2 的关联。攀爬纤维活动不影响GABAaγ2的表达。相反，它降低了丝氨酸磷酸化。攀爬纤维放电降低了 GABARAP 的表达和 GABAaγ2 的丝氨酸磷酸化。因此，攀爬纤维活性可能会降低浦肯野细胞中 GABAa 受体的表面表达，从而使浦肯野细胞不易受到神经元间 GABA 能抑制的影响。
Sustained neuronal activity induces synaptic remodeling, in part, by altering gene expression. We have used a major climbing fiber pathway onto cerebellar Purkinje cells to investigate the effects of sustained climbing fiber-evoked glutamatergic synaptic transmission on transcription, expression and phosphorylation of proteins related to the regulation of inhibitory GABAa receptor function. Binocular horizontal optokinetic stimulation was used to modulate climbing fiber signals to Purkinje cells in the flocculus and nodulus of rabbits and mice. Purkinje cells in the flocculus and nodulus ipsilateral to the eye stimulated in the Posterior → Anterior direction received increased climbing fiber activity. Purkinje cells in flocculus and nodulus ipsilateral to the eye stimulated in the Anterior → Posterior direction received decreased climbing fiber activity. We identified changes in levels of gene transcripts in floccular and nodular Purkinje cells with the technique of differential display RT-PCR. Increased climbing fiber input reduced transcript levels and expression of GABA receptor-associated protein (GABARAP). Using a protein ‘pull down’ technique, we showed that GABARAP interacts with serine phosphorylated GABAaγ2, gephyrin and β-tubulin. Serine de-phosphorylation of GABAaγ2 reduced association of GABARAP with GABAaγ2. Climbing fiber activity did not influence the expression of GABAaγ2. Rather, it decreased its serine phosphorylation. Climbing fiber discharge decreased both expression of GABARAP and serine phosphorylation of GABAaγ2. Consequently, climbing fiber activity may reduce the surface expression of GABAa receptors in Purkinje cells rendering Purkinje cells less susceptible to interneuronal GABAergic inhibition.
登录
查看更多内容
影响因子：
4.8
作者：
Brandon, NJ;Delmas, P;Moss, SJ
通讯作者：
Moss, SJ
影响因子：
25
作者：
Essrich, C;Lorez, M;Lüscher, B
通讯作者：
Lüscher, B
影响因子：
16.2
作者：
KRISHEK, BJ;XIE, XM;SMART, TG
通讯作者：
SMART, TG
影响因子：
5.5
作者：
BLISS, TVP;LOMO, T
通讯作者：
LOMO, T
影响因子：
5.5
作者：
ITO, M;SAKURAI, M;TONGROACH, P
通讯作者：
TONGROACH, P