Differential trafficking of AMPA and NMDA receptors by SAP102 and PSD-95 underlies synapse development
Differential trafficking of AMPA and NMDA receptors by SAP102 and PSD-95 underlies synapse development
复制标题
DOI：
10.1073/pnas.0811025106
复制
发表时间：
2008-12-30
影响因子：
11.1
通讯作者：
Nicoll, R. A.
中科院分区：
文献类型：
--
作者：
Elias, G. M.;Elias, L. A. B.;Nicoll, R. A.
突触能突触的发育涉及突触后密度受体的数量和类型的变化。为了阐明这些变化背后的分子机制，我们结合联合收割机在子宫内电穿孔的结构，改变双全细胞电生理学发育突触的分子组成，检查突触传递在两个不同的发育阶段。我们发现，SAP 102介导的AMPA和NMDA受体在突触形成的突触运输。令人惊讶的是，在突触发生后，PSD-95承担了SAP 102的功能，并且对于突触成熟的两个方面是必需的：AMPA受体传递的发育增加和NR 2A-NMDAR取代NR 2B-NMDAR。在PSD-95/PSD-93双KO小鼠中，NR 2A-NMDAR对NR 2B-的成熟取代未能发生，PSD-95表达完全挽救了这种缺陷。这项研究表明，SAP 102和PSD-95调节不同的谷氨酸受体亚型在不同的发育阶段的突触运输，从而在兴奋性突触发育中发挥必要的作用。
The development of glutamatergic synapses involves changes in the number and type of receptors present at the postsynaptic density. To elucidate molecular mechanisms underlying these changes, we combine in utero electroporation of constructs that alter the molecular composition of developing synapses with dual whole-cell electrophysiology to examine synaptic transmission during two distinct developmental stages. We find that SAP102 mediates synaptic trafficking of AMPA and NMDA receptors during synaptogenesis. Surprisingly, after synaptogenesis, PSD-95 assumes the functions of SAP102 and is necessary for two aspects of synapse maturation: the developmental increase in AMPA receptor transmission and replacement of NR2B-NMDARs with NR2A-NMDARs. In PSD-95/PSD-93 double-KO mice, the maturational replacement of NR2B- with NR2A-NMDARs fails to occur, and PSD-95 expression fully rescues this deficit. This study demonstrates that SAP102 and PSD-95 regulate the synaptic trafficking of distinct glutamate receptor subtypes at different developmental stages, thereby playing necessary roles in excitatory synapse development.