Subunit-specific regulation of NMDA receptor endocytosis
Subunit-specific regulation of NMDA receptor endocytosis
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DOI：
10.1523/jneurosci.1890-04.2004
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发表时间：
2004-07-14
影响因子：
5.3
通讯作者：
Roche, KW
中科院分区：
文献类型：
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作者：
Lavezzari, G;McCallum, J;Roche, KW
在兴奋性突触，NMDA和AMPA受体都定位于突触后密度（PSD）。然而，与AMPA受体不同，突触NMDA受体是PSD的稳定组分。即便如此，表面表达的NMDA受体也会经历内吞作用，这种内吞作用在发育早期更为强烈，在突触发育期间则会减弱。我们研究了亚基特异性对NMDA受体内吞作用的贡献，具体定义了NR2A和NR2B亚基偏好的内吞基序和内吞途径。我们发现NR2A和NR2B在其远端C端编码有不同的内吞基序，并且这些基序与网格蛋白接头复合物以不同的亲和力相互作用。我们还发现NR2A和NR2B在内吞作用后进入不同的细胞内通路，NR2B优先通过回收内体转运。在成熟的培养中，我们发现NR2B比NR2A经历更强大的内吞作用，这与之前的研究一致，NR2A在稳定的突触部位表达更高。我们的研究结果证明了NR2A和NR2B之间的根本差异，这有助于阐明NMDA受体转运和表面表达的发育变化。
At excitatory synapses, both NMDA and AMPA receptors are localized to the postsynaptic density (PSD). However, unlike AMPA receptors, synaptic NMDA receptors are stable components of the PSD. Even so, surface-expressed NMDA receptors undergo endocytosis, which is more robust early in development and declines during synaptic development. We investigated the subunit-specific contributions to NMDA receptor endocytosis, specifically defining the endocytic motifs and endocytic pathways preferred by the NR2A and NR2B subunits. We find that NR2A and NR2B have distinct endocytic motifs encoded in their distal C termini and that these interact with clathrin adaptor complexes with differing affinities. We also find that NR2A and NR2B sort into different intracellular pathways after endocytosis, with NR2B preferentially trafficking through recycling endosomes. In mature cultures, we find that NR2B undergoes more robust endocytosis than NR2A, consistent with previous studies showing that NR2A is more highly expressed at stable synaptic sites. Our findings demonstrate fundamental differences between NR2A and NR2B that help clarify developmental changes in NMDA receptor trafficking and surface expression.