Regulation of SAP102 Synaptic Targeting by Phosphorylation.
Regulation of SAP102 Synaptic Targeting by Phosphorylation.
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DOI：
10.1007/s12035-017-0836-4
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发表时间：
2018-08
影响因子：
5.1
通讯作者：
Chen BS
中科院分区：
文献类型：
--
作者：
Wei Z;Wu G;Chen BS
突触相关蛋白102（SAP 102）是一种在发育早期高度表达的支架蛋白，在突触发生过程中介导谷氨酸受体运输中起关键作用。据报道，人SAP 102中的突变会导致智力残疾，这被认为是由于突变蛋白的错误定位。然而，对SAP 102突触靶向的调控知之甚少。在这里，我们调查SAP 102的磷酸化在调节其突触靶向的作用。先前的研究表明，SAP 102的突触靶向是由C末端剪接调节的。我们现在确定了一个磷酸化位点，丝氨酸632，在C-末端可变剪接区，这是由酪蛋白激酶II（CK 2）磷酸化。我们发现，SAP 102上的ser 632在体外，异源细胞和神经元中被磷酸化。此外，我们证明，突触富集SAP 102增加ser 632磷酸化。因此，抑制ser 632磷酸化的突触活性的升高减少了SAP 102的突触富集。此外，SAP 102的迁移率降低ser 632磷酸化。因此，不仅SAP 102突触靶向，而且其移动性也受到Ser 632磷酸化的调节。这些数据提供了一个新的机制，在调节SAP 102功能和谷氨酸受体运输的证据。
Synapse-associated protein 102 (SAP102) is a scaffolding protein highly expressed early in development and plays a critical role in mediating glutamate receptor trafficking during synaptogenesis. Mutations in human SAP102 have been reported to cause intellectual disability, which is thought to be due to mis-localization of the mutant protein. However, little is known about the regulation of SAP102 synaptic targeting. Here we investigate the role of phosphorylation of SAP102 in regulating its synaptic targeting. Previous studies have shown that synaptic targeting of SAP102 is regulated by C-terminal splicing. We now identify a phosphorylation site, serine 632, within the C-terminal alternatively spliced region, which is phosphorylated by casein kinase II (CK2). We show that ser632 on SAP102 is phosphorylated in vitro, in heterologous cells, and in neurons. Moreover, we demonstrate that synaptic enrichment of SAP102 is increased by ser632 phosphorylation. Consistently, elevation of synaptic activity that suppresses ser632 phosphorylation reduces synaptic enrichment of SAP102. Furthermore, the mobility of SAP102 is decreased by ser632 phosphorylation. Therefore, not only SAP102 synaptic targeting but also its mobility is regulated by Ser632 phosphorylation. These data provide evidence for a novel mechanism in regulating SAP102 function and glutamate receptor trafficking.
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DOI：
10.1523/jneurosci.4457-06.2007
发表时间：
2007-03-07
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
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通讯作者：
Grant SG
DOI：
10.1523/jneurosci.1034-10.2011
发表时间：
2011-01-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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作者：
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通讯作者：
Roche KW
DOI：
10.1073/pnas.0811025106
发表时间：
2008-12-30
影响因子：
11.1
作者：
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通讯作者：
Nicoll, R. A.
影响因子：
16.2
作者：
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通讯作者：
Nicoll, Roger A.
影响因子：
9.8
作者：
Tarpey, P;Parnau, J;Raymond, FL
通讯作者：
Raymond, FL