STEP activation by Gαq coupled GPCRs opposes Src regulation of NMDA receptors containing the GluN2A subunit.
STEP activation by Gαq coupled GPCRs opposes Src regulation of NMDA receptors containing the GluN2A subunit.
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DOI：
10.1038/srep36684
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发表时间：
2016-11-18
影响因子：
4.6
通讯作者：
MacDonald JF
中科院分区：
文献类型：
--
作者：
Tian M;Xu J;Lei G;Lombroso PJ;Jackson MF;MacDonald JF
N-甲基-D-天冬氨酸受体（NMDAR）是诱导突触可塑性和巩固学习和记忆所必需的。NMDAR功能受到功能上相反的激酶和磷酸酶家族的严格调节。在此，我们发现纹状体富集蛋白酪氨酸磷酸酶（STEP）被Gα q偶联受体（包括M1毒蕈碱乙酰胆碱受体（M1 R））募集，并对抗Src酪氨酸激酶介导的由GluN 2A组成的NMDAR功能的增加。通过M1 R刺激的STEP激活需要IP 3R，并且可以用适度的细胞内Ca 2+缓冲来抑制NMDA诱发的电流。M1 R刺激的Src募集需要同时的NMDAR激活，并且可以通过高细胞内Ca 2+缓冲来增加NMDA诱发的电流。我们的研究结果表明，Src和STEP的招聘是偶然的不同的细胞内Ca 2+动态，决定是否NMDAR功能增强或抑制后M1 R刺激。
N-methyl-D-aspartate receptors (NMDARs) are necessary for the induction of synaptic plasticity and for the consolidation of learning and memory. NMDAR function is tightly regulated by functionally opposed families of kinases and phosphatases. Herein we show that the striatal-enriched protein tyrosine phosphatase (STEP) is recruited by Gαq-coupled receptors, including the M1 muscarinic acetylcholine receptor (M1R), and opposes the Src tyrosine kinase-mediated increase in the function of NMDARs composed of GluN2A. STEP activation by M1R stimulation requires IP3Rs and can depress NMDA-evoked currents with modest intracellular Ca2+ buffering. Src recruitment by M1R stimulation requires coincident NMDAR activation and can augment NMDA-evoked currents with high intracellular Ca2+ buffering. Our findings suggest that Src and STEP recruitment is contingent on differing intracellular Ca2+ dynamics that dictate whether NMDAR function is augmented or depressed following M1R stimulation.
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影响因子：
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作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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影响因子：
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