Trafficking of the NMDAR2B receptor subunit distal cytoplasmic tail from endoplasmic reticulum to the synapse.
Trafficking of the NMDAR2B receptor subunit distal cytoplasmic tail from endoplasmic reticulum to the synapse.
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DOI：
10.1371/journal.pone.0039585
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wenthold RJ
中科院分区：
文献类型：
--
作者：
Standley S;Petralia RS;Gravell M;Hamilton R;Wang YX;Schubert M;Wenthold RJ
NMDA受体NR2A/B亚基在其末端c端具有PDZ结合结构域，已知与PSD-95家族和其他PDZ蛋白相互作用。我们研究了PSD-95家族蛋白与NR2A/B细胞质尾部之间的相互作用，以及这些相互作用的后果，从内质网（ER）通过传递到突触，在大鼠海马和皮层培养的神经元中。我们发现NR2A/B细胞质尾部在分泌通路中很早就聚集，并从中间室开始与SAP102序列相互作用，然后是PSD-95。我们进一步确定NR2B和PSD-95的远端c端共定位始于跨高尔基网络（TGN）。NR2B/PSD-95/SAP102复合物的形成依赖于NR2B亚基的PDZ结合域，但与SAP102和PSD-95的结合在簇预形成或初始靶向突触附近没有明显的作用。相反，PDZ结合域在限制细胞表面簇到达突触后靶点方面发挥作用。
NMDA receptor NR2A/B subunits have PDZ-binding domains on their extreme C-termini that are known to interact with the PSD-95 family and other PDZ proteins. We explore the interactions between PSD-95 family proteins and the NR2A/B cytoplasmic tails, and the consequences of these interactions, from the endoplasmic reticulum (ER) through delivery to the synapse in primary rat hippocampal and cortical cultured neurons. We find that the NR2A/B cytoplasmic tails cluster very early in the secretory pathway and interact serially with SAP102 beginning at the intermediate compartment, and then PSD-95. We further establish that colocalization of the distal C-terminus of NR2B and PSD-95 begins at the trans-Golgi Network (TGN). Formation of NR2B/PSD-95/SAP102 complexes is dependent on the PDZ binding domain of NR2B subunits, but association with SAP102 and PSD-95 plays no distinguishable role in cluster pre-formation or initial targeting to the vicinity of the synapse. Instead the PDZ binding domain plays a role in restricting cell-surface clusters to postsynaptic targets.