Glutamate transporter type 3 regulates mouse hippocampal GluR1 trafficking.
Glutamate transporter type 3 regulates mouse hippocampal GluR1 trafficking.
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DOI：
10.1016/j.bbagen.2014.01.006
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发表时间：
2014-06
影响因子：
3
通讯作者：
Zuo, Zhiyi
中科院分区：
文献类型：
--
作者：
Cao, Jiangbei;Tan, Hongying;Mi, Weidong;Zuo, Zhiyi
关键词：
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic酸受体的快速转运被认为是学习和记忆的基本生物学过程。GluR1是AMPAR亚基。我们已经证明，兴奋性氨基酸转运体3(EAAT3)基因敲除的小鼠，一种神经元谷氨酸转运体，会损害学习和记忆。这种损害的机制尚不清楚，可能是通过对AMPAR贩运的监管。取野生型或EAAT3基因敲除小鼠新鲜制备的300µm海马冠状脑片，分别加入或不加入25 mM四乙基铵孵育10min。检测AMPAR亚基GluR1向质膜的转运及其磷酸化。在野生型小鼠的海马片中，四乙基铵增加了GluR1和EAAT3向质膜的转运，但在EAAT3基因敲除的小鼠中并没有引起GluR1的转运。在野生型小鼠中，四乙基铵还增加了蛋白激酶A(PKA)位点S845处GluR1的磷酸化，但在EAAT3基因敲除小鼠中没有。PKA拮抗剂KT5720可减弱四乙基铵诱导的GluR1在野生型小鼠体内的磷酸化和转运。在EAAT3基因敲除小鼠中，PKA激动剂6-BNZ-cAMP导致GluR1转运到质膜。此外，EAAT3还与PKA共沉淀。这些结果表明，EAAT3位于PKA的上游，是调节GluR1运输的途径。我们的结果为EAAT3参与学习和记忆的生化级联提供了初步证据。
Rapid trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) to the plasma membrane is considered a fundamental biological process for learning and memory. GluR1 is an AMPAR subunit. We have shown that mice with knockout of excitatory amino acid transporter type 3 (EAAT3), a neuronal glutamate transporter, have impaired learning and memory. The mechanisms for this impairment are not known and may be via regulation of AMPAR trafficking. Freshly prepared 300 µm coronal hippocampal slices from wild-type or EAAT3 knockout mice were incubated with or without 25 mM tetraethylammonium for 10 min. The trafficking of GluR1, an AMPAR subunit, to the plasma membrane and its phosphorylation were measured. Tetraethylammonium increased the trafficking of GluR1 and EAAT3 to the plasma membrane in the wild-type mouse hippocampal slices but did not cause GluR1 trafficking in the EAAT3 knockout mice. Tetraethylammonium also increased the phosphorylation of GluR1 at S845, a protein kinase A (PKA) site, in the wild-type mice but not in the EAAT3 knockout mice. The PKA antagonist KT5720 attenuated tetraethylammonium-induced GluR1 phosphorylation and trafficking in the wild-type mice. The PKA agonist 6-BNz-cAMP caused GluR1 trafficking to the plasma membrane in the EAAT3 knockout mice. In addition, EAAT3 was co-immunoprecipitated with PKA. These results suggest that EAAT3 is upstream of PKA in a pathway to regulate GluR1 trafficking. Our results provide initial evidence for the involvement of EAAT3 in the biochemical cascade of learning and memory.
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影响因子：
2.9
作者：
Jung, Hae-Hyuk;Lee, Jeong Jin;Zuo, Zhiyi
通讯作者：
Zuo, Zhiyi
影响因子：
25
作者：
Gu, Jiaping;Lee, Chi Wai;Fan, Yanjie;Komlos, Daniel;Tang, Xin;Sun, Chicheng;Yu, Kuai;Hartzell, H. Criss;Chen, Gong;Bamburg, James R.;Zheng, James Q.
通讯作者：
Zheng, James Q.
DOI：
10.1523/jneurosci.4845-09.2009
发表时间：
2009-11-18
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Scimemi A;Tian H;Diamond JS
通讯作者：
Diamond JS
影响因子：
6.3
作者：
Li, Liaoliao;Zuo, Zhiyi
通讯作者：
Zuo, Zhiyi
影响因子：
11.4
作者：
Peghini, P;Janzen, J;Stoffel, W
通讯作者：
Stoffel, W