Post-transcriptional regulation of GABAB receptor and GIRK1 channels by Nogo receptor 1.

Post-transcriptional regulation of GABAB receptor and GIRK1 channels by Nogo receptor 1.
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DOI:
10.1186/1756-6606-6-30
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发表时间:
2013-07-06
期刊:
影响因子:
3.6
通讯作者:
Mata M
Mata M
中科院分区:
医学3区
文献类型:
--
作者:
Murthy R;Kim J;Sun X;Giger RJ;Fink DJ;Mata M

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B 型 GABA 受体 (GABA R) 在突触传递中发挥着关键作用。我们进行了研究以确定 GABAB-Rs 的神经元细胞表面表达是否可能受到 Nogo 受体 1 (NgR1) 的调节。 NgR1 的 siRNA 敲低导致 GABAB R1 和 GABAB R2 蛋白选择性增加,而不改变 GABAA 受体或 GAD65 的表达。 GABAB 受体亚基的增加不伴随 mRNA 的变化,但雷帕霉素对 mTOR 的抑制阻止了 GABAB 蛋白的增加。 NgR1 siRNA 还引起 G 蛋白偶联内向整流钾通道 (GIRK1) 的增加。 GABAB 受体和 GIRK1 通道蛋白的增加位于质膜中,由细胞表面生物素化决定。在 NgR1 敲除小鼠中,海马源性突触体中 GABAB R2 和 GIRK1 的数量增加。这些发现共同表明,NgR1 介导的突触传递调节可能至少部分通过 G 蛋白偶联受体和通道的调节来完成。
Type B GABA receptors (GABA Rs) play a critical role in synaptic transmission. We carried out studies to determine whether neuronal cell surface expression of GABAB-Rs might be regulated by the Nogo receptor 1 (NgR1). siRNA knock-down of NgR1 resulted in a selective increase of GABAB R1 and GABAB R2 protein without altering the expression of GABAA receptor or GAD65. The increase in GABAB receptor subunits was unaccompanied by a change in mRNA, but inhibition of mTOR by rapamycin blocked the increase in GABAB protein. NgR1 siRNA also caused an increase in G protein coupled inwardly rectifying potassium channel (GIRK1). The increase in GABAB receptor and GIRK1 channel proteins was in the plasma membrane, determined by cell surface biotinylation. In NgR1 knockout mice, the amount of GABAB R2 and GIRK1 in hippocampus-derived synaptosomes was increased. Together these findings suggest that NgR1 mediated modulation of synaptic transmission may be accomplished, at least in part, through modulation of G protein coupled receptors and channels.
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