An NMDA receptor ER retention signal regulated by phosphorylation and alternative splicing

被引：346

作者：

Scott, DB

Blanpied, TA

Swanson, GT

Zhang, C

Ehlers, MD ^{[1
]}

机构：

[1] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA

[2] Duke Univ, Med Ctr, Cell & Mol Biol Program, Durham, NC 27710 USA

[3] Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA

来源：

JOURNAL OF NEUROSCIENCE | 2001年 / 21卷 / 09期

关键词：

ER retention; NMDA receptors; NR1; subunit; RXR motif; quality control mechanisms; intracellular trafficking;

D O I：

10.1523/JNEUROSCI.21-09-03063.2001

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Formation of mature excitatory synapses requires the assembly and delivery of NMDA receptors to the neuronal plasma membrane. A key step in the trafficking of NMDA receptors to synapses is the exit of newly assembled receptors from the endoplasmic reticulum (ER). Here we report the identification of an RXR-type ER retention/retrieval motif in the C-terminal tail of the NMDA receptor subunit NR1 that regulates receptor surface expression in heterologous cells and in neurons. In addition, we show that PKC phosphorylation and an alternatively spliced consensus type I PDZ-binding domain suppress ER retention. These results demonstrate a novel quality control function for alternatively spliced C-terminal domains of NR1 and implicate both phosphorylation and potential PDZ-mediated interactions in the trafficking of NMDA receptors through early stages of the secretory pathway.

引用

页码：3063 / 3072

页数：10