Regulation of AMPA receptor-mediated synaptic transmission by clathrin-dependent receptor internalization
Regulation of AMPA receptor-mediated synaptic transmission by clathrin-dependent receptor internalization
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DOI：
10.1016/s0896-6273(00)81067-3
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发表时间：
2000-03-01
期刊：
影响因子：
16.2
通讯作者：
Wang, YT
中科院分区：
文献类型：
--
作者：
Man, HY;Lin, JW;Wang, YT
突触后AMPA-（α-氨基-3-羟基-5-甲基异恶唑-4-丙酸-）亚型谷氨酸受体的再分布可能调节突触强度在谷氨酸能突触，但介导的再分布知之甚少。我们发现，AMPA受体进行网格蛋白依赖的内吞作用，这是加速胰岛素在GluR 2亚基依赖的方式。胰岛素刺激的内吞作用迅速减少质膜中AMPA受体的数量，导致海马CA 1区神经元中AMPA受体介导的突触传递的长期抑制（LTD）。此外，胰岛素诱导的LTD和低频刺激（LFS-）诱导的同突触CA 1 LTD被发现是相互闭塞的，都被阻断抑制突触后网格蛋白介导的内吞作用。因此，通过内吞作用控制突触后受体数量可能是哺乳动物中枢神经系统突触可塑性的重要机制。
Redistribution of postsynaptic AMPA- (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-) subtype glutamate receptors may regulate synaptic strength at glutamatergic synapses, but the mediation of the redistribution is poorly understood. We show that AMPA receptors underwent clathrin-dependent endocytosis, which was accelerated by insulin in a GluR2 subunit-dependent manner. Insulin-stimulated endocytosis rapidly decreased AMPA receptor numbers in the plasma membrane, resulting in long-term depression (LTD) of AMPA receptor-mediated synaptic transmission in hippocampal CA1 neurons. Moreover, insulin-induced LTD and low-frequency stimulation-(LFS-) induced homosynaptic CA1 LTD were found to be mutually occlusive and were both blocked by inhibiting postsynaptic clathrin-mediated endocytosis. Thus, controlling postsynaptic receptor numbers through endocytosis may be an important mechanism underlying synaptic plasticity in the mammalian CNS.