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SAP97和CASK通过一条此前未知的分泌途径介导N-甲基-D-天冬氨酸受体的分选。

SAP97 and CASK mediate sorting of NMDA receptors through a previously unknown secretory pathway.

作者信息

Jeyifous Okunola, Waites Clarissa L, Specht Christian G, Fujisawa Sho, Schubert Manja, Lin Eric I, Marshall John, Aoki Chiye, de Silva Tharani, Montgomery Johanna M, Garner Craig C, Green William N

机构信息

Department of Psychiatry and Behavioral Science, Stanford University, Palo Alto, California, USA.

出版信息

Nat Neurosci. 2009 Aug;12(8):1011-9. doi: 10.1038/nn.2362. Epub 2009 Jul 20.

DOI:10.1038/nn.2362
PMID:19620977
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2779056/
Abstract

Synaptic plasticity is dependent on the differential sorting, delivery and retention of neurotransmitter receptors, but the mechanisms underlying these processes are poorly understood. We found that differential sorting of glutamate receptor subtypes began in the endoplasmic reticulum of rat hippocampal neurons. As AMPA receptors (AMPARs) were trafficked to the plasma membrane via the conventional somatic Golgi network, NMDA receptors (NMDARs) were diverted from the somatic endoplasmic reticulum into a specialized endoplasmic reticulum subcompartment that bypasses somatic Golgi, merging instead with dendritic Golgi outposts. This endoplasmic reticulum subcompartment was composed of highly mobile vesicles containing the NMDAR subunits NR1 and NR2B, the microtubule-dependent motor protein KIF17, and the postsynaptic adaptor proteins CASK and SAP97. Our data demonstrate that the retention and trafficking of NMDARs in this endoplasmic reticulum subcompartment requires both CASK and SAP97. These findings indicate that NMDARs are sorted away from AMPARs via a non-conventional secretory pathway that utilizes dendritic Golgi outposts.

摘要

突触可塑性依赖于神经递质受体的差异分选、运输和保留，但这些过程背后的机制仍知之甚少。我们发现谷氨酸受体亚型的差异分选始于大鼠海马神经元的内质网。当α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPARs）通过传统的胞体高尔基体网络运输到质膜时，N-甲基-D-天冬氨酸受体（NMDARs）从胞体内质网转移到一个特殊的内质网亚区室，该亚区室绕过胞体高尔基体，而是与树突状高尔基体前哨融合。这个内质网亚区室由含有NMDAR亚基NR1和NR2B、微管依赖性运动蛋白驱动蛋白17（KIF17）以及突触后衔接蛋白钙/钙调蛋白依赖性丝氨酸蛋白激酶（CASK）和突触相关蛋白97（SAP97）的高度移动的囊泡组成。我们的数据表明，NMDARs在这个内质网亚区室中的保留和运输需要CASK和SAP97。这些发现表明，NMDARs通过利用树突状高尔基体前哨的非常规分泌途径与AMPARs分选开来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a80e/2779056/fde51fbdf80e/nihms122984f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a80e/2779056/ec9555c952a0/nihms122984f1a.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a80e/2779056/07222e5d86f7/nihms122984f3a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a80e/2779056/b4ce24b05645/nihms122984f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a80e/2779056/0623cd9e2cd0/nihms122984f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a80e/2779056/126ebdad7bb5/nihms122984f6a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a80e/2779056/fde51fbdf80e/nihms122984f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a80e/2779056/ec9555c952a0/nihms122984f1a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a80e/2779056/28ed2f9dc0fa/nihms122984f2a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a80e/2779056/07222e5d86f7/nihms122984f3a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a80e/2779056/b4ce24b05645/nihms122984f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a80e/2779056/0623cd9e2cd0/nihms122984f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a80e/2779056/126ebdad7bb5/nihms122984f6a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a80e/2779056/fde51fbdf80e/nihms122984f7.jpg

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