SARS-CoV-1基因组复制
中文名称
通路描述
人类SARS冠状病毒1（SARS-CoV-1）的+链RNA基因组由病毒复制转录复合物（RTC）复制，该复合物由非结构蛋白nsp3-nsp16组成，由开放阅读框ORF1a和ORF1b编码。两个RTC蛋白nsp8和nsp12具有5'-3' RNA依赖的RNA聚合酶活性。nsp12是主要RNA聚合酶，而nsp8被认为充当RNA引物酶。nsp14具有3'-5'外切酶活性，提高了RTC的保真度。nsp14还具有RNA加帽活性，与nsp16协同作用，对病毒+链和-链基因组及亚基因组RNA进行加帽，从而通过使病毒RNA能够逃避免疫介导的宿主先天免疫反应而赋予病毒RNA稳定性。nsp13是一种RNA解旋酶，被认为在复制和转录过程中熔解基因组RNA中的二级结构。+链基因组RNA首先用于合成-链基因组RNA互补链，随后作为模板合成+链病毒RNA基因组，这些基因组被包装到成熟病毒颗粒中。如需综述，请参考Yang和Leibowitz 2015, Snijder等人 2016, Fung和Liu 2019。
英文描述
Assembly and cell surface presentation of NMDA receptors N-methyl-D-aspartate receptors (NMDARs) are tetramers that consist of two GluN1 (GRIN1) subunits and two subunits that belong to either the GluN2 (GRIN2) subfamily (GluN2A, GluN2B, GluN2C and GluN2D) or the GluN3 (GRIN3) subfamily (GluN3A and GluN3B). The GluN2/GluN3 subunits in the NMDA tetramer can either be identical, constituting an NMDA di-heteromer (di-heterotetramer), which consists of two subunit types, GluN1 and one of GluN2s/GluN3s, or they can be two different GluN2/GluN3 proteins, constituting an NMDA tri-heteromer (tri-heterotetramer), which consists of three subunit types, GluN1 and two of GluN2s/GluN3s (Monyer et al. 1992, Wafford et al. 1993, Sheng et al. 1994, Dunah et al. 1998, Perez-Otano et al. 2001, Chatterton et al. 2002, Matsuda et al. 2002, Yamakura et al. 2005, Nilsson et al. 2007, Hansen et al. 2014, Kaiser et al. 2018, Bhattacharya et al. 2018, Bhattacharya and Traynelis 2018).
NMDA tetramers assemble in the endoplasmic reticulum and traffic to the plasma membrane as part of transport vesicles (McIlhinney et al. 1998, Perez-Otano et al. 2001). NMDA receptor subunits undergo N-glycosylation, which impacts their trafficking from the endoplasmic reticulum to the plasma membrane. Trafficking efficiency may vary among different subunits of NMDARs (Lichnereva et al. 2015). Mechanistic details, such as glycosyl transferases involved and the type of sugar side chains added, are not known.
As there are eight splicing isoforms of GluN1, four different GluN2 and two different GluN3 proteins, many different combinations of NMDAR subunits are possible, but only a handful of distinct NMDAR receptors have been experimentally confirmed and functionally studied. The composition of NMDARs affects trafficking, spatial (including synaptic) localization, ligand preference, channel conductivity and downstream signal transmission. Prevalent NMDARs differ at different stages of neuronal development, in different regions of the central nervous system, and at different levels of neuronal activity. For review, please refer to Lau and Zukin 2007, Traynelis et al. 2010, Paoletti et al. 2013, Pérez-Otaño et al. 2016, Iacobucci and Popescu 2017.
NMDA tetramers assemble in the endoplasmic reticulum and traffic to the plasma membrane as part of transport vesicles (McIlhinney et al. 1998, Perez-Otano et al. 2001). NMDA receptor subunits undergo N-glycosylation, which impacts their trafficking from the endoplasmic reticulum to the plasma membrane. Trafficking efficiency may vary among different subunits of NMDARs (Lichnereva et al. 2015). Mechanistic details, such as glycosyl transferases involved and the type of sugar side chains added, are not known.
As there are eight splicing isoforms of GluN1, four different GluN2 and two different GluN3 proteins, many different combinations of NMDAR subunits are possible, but only a handful of distinct NMDAR receptors have been experimentally confirmed and functionally studied. The composition of NMDARs affects trafficking, spatial (including synaptic) localization, ligand preference, channel conductivity and downstream signal transmission. Prevalent NMDARs differ at different stages of neuronal development, in different regions of the central nervous system, and at different levels of neuronal activity. For review, please refer to Lau and Zukin 2007, Traynelis et al. 2010, Paoletti et al. 2013, Pérez-Otaño et al. 2016, Iacobucci and Popescu 2017.
所含基因
43 个基因