Man H Y, Lin J W, Ju W H, Ahmadian G, Liu L, Becker L E, Sheng M, Wang Y T
Division of Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Neuron. 2000 Mar;25(3):649-62. doi: 10.1016/s0896-6273(00)81067-3.
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.
突触后α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）亚型谷氨酸受体的重新分布可能会调节谷氨酸能突触的突触强度，但对这种重新分布的介导机制却知之甚少。我们发现，AMPA受体经历了网格蛋白依赖的内吞作用，胰岛素以依赖GluR2亚基的方式加速了这一过程。胰岛素刺激的内吞作用迅速减少了质膜上AMPA受体的数量，导致海马CA1神经元中AMPA受体介导的突触传递出现长时程抑制（LTD）。此外，发现胰岛素诱导的LTD和低频刺激（LFS）诱导的同突触CA1 LTD相互阻塞，并且两者都可通过抑制突触后网格蛋白介导的内吞作用而被阻断。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中突触可塑性的重要潜在机制。
