Homer-dependent cell surface expression of metabotropic glutamate receptor type 5 in neurons
Homer-dependent cell surface expression of metabotropic glutamate receptor type 5 in neurons
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DOI：
10.1006/mcne.2002.1100
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发表时间：
2002-06-01
影响因子：
3.5
通讯作者：
Fagni, L
中科院分区：
文献类型：
--
作者：
Ango, F;Robbe, D;Fagni, L
代谢型谷氨酸（mGlu）受体是参与调节脑中快速兴奋性突触传递的受体家族。在异源表达系统中进行的实验表明，I组mGlu受体的细胞表面表达受其辅助蛋白Homer控制。然而，这是否也适用于神经元仍然存在争议。在这里，我们表明，在培养的小脑颗粒细胞，组I mGlu受体亚型，mGlu5，单独转染的功能表达在这些神经元的表面。转染Homer1b引起细胞内滞留和聚集这种受体在突触部位。单独重组Homer1a不影响细胞表面受体的表达，但在转染Homer1b的神经元中，兴奋诱导的天然Homer1a表达逆转了mGlu5受体的细胞内滞留，导致受体转运至突触膜。转染Homer1a还增加了mGlu5受体Ca2+反应的潜伏期和振幅。这些结果表明，Homer1蛋白调节突触周期和钙离子信号的mGlu5受体，响应神经元的活动。
The metabotropic glutamate (mGlu) receptors are a family of receptors involved in the tuning of fast excitatory synaptic transmission in the brain. Experiments performed in heterologous expression systems suggest that cell surface expression of group I mGlu receptors is controlled by their auxiliary protein, Homer. However, whether or not this also applies to neurons remains controversial. Here we show that in cultured cerebellar granule cells, the group I mGlu receptor subtype, mGlu5, transfected alone is functionally expressed at the surface of these neurons. Transfected Homer1b caused intracellular retention and clustering of this receptor at synaptic sites. Recombinant Homer1a alone did not affect cell surface expression of the receptor, but in neurons transfected with Homer1b, excitation-induced expression of native Homer1a reversed the intracellular retention of mGlu5 receptors, resulting in the receptor trafficking to synaptic membranes. Transfected Homer1a also increased the latency and amplitude of the mGlu5 receptor Ca2+ response. These results indicate that Homer1 proteins regulate synaptic cycling and Ca2+ signaling of mGlu5 receptors, in response to neuronal activity.