Reinsertion or degradation of AMPA receptors determined by activity-dependent endocytic sorting
Reinsertion or degradation of AMPA receptors determined by activity-dependent endocytic sorting
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DOI：
10.1016/s0896-6273(00)00129-x
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发表时间：
2000-11-01
期刊：
影响因子：
16.2
通讯作者：
Ehlers, MD
中科院分区：
文献类型：
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作者：
Ehlers, MD
AMPA受体（AMPAR）定位的急性和慢性变化对于突触的形成、成熟和可塑性都至关重要。在此我报道，在胞吞作用之后，AMPAR在再循环和降解途径之间存在差异性分选。AMPAR分选发生在早期内体中，并受突触活动以及AMPA和NMDA受体的激活所调节。由NMDAR激活引发的AMPAR内化是Ca2+依赖性的，需要蛋白磷酸酶，并且随后会快速重新插入细胞膜。此外，NMDAR介导的AMPAR运输受PKA调节，并伴随着GluR1亚基在一个PKA位点的去磷酸化和再磷酸化。相反，在没有NMDAR激活的情况下激活AMPAR会使AMPAR靶向晚期内体和溶酶体，这一过程不依赖于Ca2+、蛋白磷酸酶或PKA。这些结果表明，活动调节AMPAR的胞吞分选，为突触强度的快速和慢性变化之间提供了一种潜在的机制联系。
Both acute and chronic changes in AMPA receptor (AMPAR) localization are critical for synaptic formation, maturation, and plasticity. Here I report that AMPARs are differentially sorted between recycling and degradative pathways following endocytosis. AMPAR sorting occurs in early endosomes and is regulated by synaptic activity and activation of AMPA and NMDA receptors. AMPAR internalization triggered by NMDAR activation is Ca2+-dependent, requires protein phosphatases, and is followed by rapid membrane reinsertion. Furthermore, NMDAR-mediated AMPAR trafficking is regulated by PKA and accompanied by dephosphorylation and rephosphorylation of GluR1 subunits at a PKA site. In contrast, activation of AMPARs without NMDAR activation targets AMPARs to late endosomes and lysosomes, independent of Ca2+, protein phosphatases, or PKA. These results demonstrate that activity regulates AMPAR endocytic sorting, providing a potential mechanistic link between rapid and chronic changes in synaptic strength.