Role of protein kinase C phosphorylation in rapid desensitization of metabotropic glutamate receptor 5
Role of protein kinase C phosphorylation in rapid desensitization of metabotropic glutamate receptor 5
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DOI：
10.1016/s0896-6273(00)80442-0
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发表时间：
1998-01-01
期刊：
影响因子：
16.2
通讯作者：
Heinemann, SF
中科院分区：
文献类型：
--
作者：
Gereau, RW;Heinemann, SF
代谢性谷氨酸受体（mGluRs）偶联磷酸化肌肽水解在长时间或重复激动剂暴露的反应中脱敏，证据表明这涉及蛋白激酶C （PKC）的激活。目前的研究是为了确定克隆的mGluR5是否经历类似的pkc介导的脱敏，并研究pkc诱导脱敏的分子机制。在非洲爪蟾卵母细胞中，mGluR5a和mGluR5b在谷氨酸的短暂激活下均表现出明显的脱敏反应。药理学研究清楚地表明，这种脱敏需要pkc介导的磷酸化。对PKC一致磷酸化位点突变体的分析表明，PKC在多个位点磷酸化mGluR5，以诱导相对快速的脱敏形式。由于mGluRs在突触可塑性和兴奋性毒性中发挥重要作用，这种脱敏可能参与了这些过程的动态调节。
Metabotropic glutamate receptors (mGluRs) coupled to phosphoinositide hydrolysis desensitize in response to prolonged or repeated agonist exposure, and evidence suggests that this involves activation of protein kinase C (PKC). The present studies were undertaken to determine if cloned mGluR5 undergoes similar PKC-mediated desensitization and to investigate the molecular mechanism underlying PKC-induced desensitization. In Xenopus oocytes, both mGluR5a and mGluR5b showed pronounced desensitization in response to a brief activation by glutamate. Pharmacological studies clearly suggest that this desensitization requires PKC-mediated phosphorylation. Analysis of PKC consensus phosphorylation site mutants suggests that PKC phosphorylates mGluR5 at multiple sites to induce a relatively rapid form of desensitization. Because mGluRs play important roles in synaptic plasticity and in excitotoxicity, this desensitization may be involved in the dynamic regulation of these processes.