Palmitoylation at two cysteine clusters on the C-terminus of GluN2A and GluN2B differentially control synaptic targeting of NMDA receptors.
Palmitoylation at two cysteine clusters on the C-terminus of GluN2A and GluN2B differentially control synaptic targeting of NMDA receptors.
复制标题
在Glun2a和Glun2b的C端两个半胱氨酸簇的棕榈酰化和NMDA受体的突触靶向。
DOI：
10.1371/journal.pone.0049089
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Barria A
中科院分区：
文献类型：
--
作者：
Mattison HA;Hayashi T;Barria A
NMDAR的棕榈酰化发生在GluN2A和GluN2B亚基的羧基末端的两个不同的半胱氨酸簇，其差异调节NMDAR在高尔基体中的保留和表面表达。近膜簇中的棕榈酰化半胱氨酸残基突变为非棕榈酰化丝氨酸导致重组NMDAR的表面表达通过增强受体的内化而减少。GluN2A和GluN2B羧基端中间的一簇半胱氨酸突变通过增加高尔基体后运输导致NMDAR表面表达增加。使用定量电生理分析，我们调查是否棕榈酰化的GluN2亚基和表面表达的差异调节影响功能性突触纳入NMDARs。我们发现，由于近膜簇突变导致的表面表达减少转化为NMDAR突触表达的减少。然而，由调节NMDAR的高尔基体后运输的半胱氨酸簇中的突变诱导的表面表达增加并不增加NMDA受体的突触池，表明突触受体的数量受到严格调节。
Palmitoylation of NMDARs occurs at two distinct cysteine clusters in the carboxyl-terminus of GluN2A and GluN2B subunits that differentially regulates retention in the Golgi apparatus and surface expression of NMDARs. Mutations of palmitoylatable cysteine residues in the membrane-proximal cluster to non-palmitoylatable serines leads to a reduction in the surface expression of recombinant NMDARs via enhanced internalization of the receptors. Mutations in a cluster of cysteines in the middle of the carboxyl-terminus of GluN2A and GluN2B, leads to an increase in the surface expression of NMDARs via an increase in post-Golgi trafficking. Using a quantitative electrophysiological assay, we investigated whether palmitoylation of GluN2 subunits and the differential regulation of surface expression affect functional synaptic incorporation of NMDARs. We show that a reduction in surface expression due to mutations in the membrane-proximal cluster translates to a reduction in synaptic expression of NMDARs. However, increased surface expression induced by mutations in the cluster of cysteines that regulates post-Golgi trafficking of NMDARs does not increase the synaptic pool of NMDA receptors, indicating that the number of synaptic receptors is tightly regulated.
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DOI：
10.1523/jneurosci.4022-09.2010
发表时间：
2010-02-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Foster KA;McLaughlin N;Edbauer D;Phillips M;Bolton A;Constantine-Paton M;Sheng M
通讯作者：
Sheng M
影响因子：
16.2
作者：
Hayashi, Takashi;Thomas, Gareth M.;Huganir, Richard L.
通讯作者：
Huganir, Richard L.
影响因子：
16.2
作者：
Barria, A;Malinow, R
通讯作者：
Malinow, R
DOI：
10.1073/pnas.1012676108
发表时间：
2011-04-05
影响因子：
11.1
作者：
Gambrill, Abigail C.;Barria, Andres
通讯作者：
Barria, Andres
影响因子：
56.9
作者：
Hayashi, Y;Shi, SH;Malinow, R
通讯作者：
Malinow, R