Cao Qianqian, Wang Zheng, Wan Huida, Xu Lijiao, You Xue, Liao Lujian, Chen Yan
CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.
iScience. 2018 Nov 30;9:382-398. doi: 10.1016/j.isci.2018.11.002. Epub 2018 Nov 4.
Endoplasmic reticulum (ER)-to-Golgi anterograde transport is driven by COPII vesicles mainly composed of a Sec23/Sec24 inner shell and a Sec13/Sec31 outer cage. How COPII vesicles are tethered to the Golgi is not completely understood. We demonstrated here that PAQR3 can facilitate tethering of COPII vesicles to the Golgi. Proximity labeling using PAQR3 fused with APEX2 identified that many proteins involved in intracellular transport are in close proximity to PAQR3. ER-to-Golgi trafficking of N-acetylgalactosaminyltransferase-2 on removal of brefeldin A is delayed by PAQR3 deletion. RUSH assay also revealed that ER-to-Golgi trafficking is affected by PAQR3. The N-terminal end of PAQR3 can interact with the WD domains of Sec13 and Sec31A. PAQR3 enhances Golgi localization of Sec13 and Sec31A. Furthermore, PAQR3 is localized in the ERGIC and cis-Golgi structures, the acceptor sites for COPII vesicles. Taken together, our study uncovers a role for PAQR3 as a player in regulating ER-to-Golgi transport of COPII vesicles.
内质网（ER）到高尔基体的顺向转运由主要由Sec23/Sec24内壳和Sec13/Sec31外壳组成的COPII囊泡驱动。COPII囊泡如何与高尔基体拴系尚不完全清楚。我们在此证明，PAQR3可促进COPII囊泡与高尔基体的拴系。使用与APEX2融合的PAQR3进行邻近标记发现，许多参与细胞内运输的蛋白质与PAQR3紧密相邻。去除布雷菲德菌素A后，N-乙酰半乳糖胺基转移酶-2从内质网到高尔基体的运输因PAQR3缺失而延迟。RUSH分析还表明，内质网到高尔基体的运输受PAQR3影响。PAQR3的N末端可与Sec13和Sec31A的WD结构域相互作用。PAQR3增强了Sec13和Sec31A在高尔基体的定位。此外，PAQR3定位于内质网-高尔基体中间区室（ERGIC）和顺式高尔基体结构，即COPII囊泡的受体位点。综上所述，我们的研究揭示了PAQR3在调节COPII囊泡从内质网到高尔基体运输中的作用。
