SMGL-1/NBAS acts as a RAB-8 GEF to regulate unconventional protein secretion.
SMGL-1/NBAS acts as a RAB-8 GEF to regulate unconventional protein secretion.
复制标题
SMGL-1/NBAS 作为 RAB-8 GEF 调节非常规蛋白分泌
DOI：
10.1083/jcb.202111125
复制
发表时间：
2022-07-04
影响因子：
7.8
通讯作者：
Lin, Long
中科院分区：
文献类型：
--
作者：
Wang, Xianghong;Li, Xinxin;Wang, Junkai;Wang, Jiabin;Hu, Can;Zeng, Jia;Shi, Anbing;Lin, Long
非常规蛋白质分泌（UPS）介导蛋白质胞吐，而不进入ER-高尔基体分泌途径。在此，Wang等人报道了SMGL-1作为RAB-8的鸟嘌呤核苷酸交换因子，以促进秀丽隐杆线虫肠上皮中整合蛋白的顶端UPS。非常规蛋白质分泌（UPS）途径在物种间是保守的。然而，潜在的机制，调节高尔基体绕过UPS的整合蛋白仍然难以捉摸。在这项研究中，我们发现RAB-8和SMGL-1/NBAS是C.线虫肠SMGL-1位于ER-高尔基体中间室和邻近的RAB-8阳性结构中，NRZ复合体组分CZW-1/ZW 10是这种驻留所必需的。值得注意的是，SMGL-1作为RAB-8的鸟嘌呤核苷酸交换因子，通过驱动RAB-8的活化来确保整合蛋白的UPS。此外，我们发现，铜绿假单胞菌感染提高SMGL-1和RAB-8的表达。SMGL-1或RAB-8的丧失损害了对环境秋水仙素、亚砷酸盐和致病菌的抗性。这些结果表明，SMGL-1/RAB-8介导的UPS可以整合环境信号，作为宿主的防御反应。通过建立C. elegans肠作为一个多细胞模型，我们的研究结果提供了深入了解RAB-8依赖高尔基体旁路UPS，特别是在上皮细胞在体内的情况。
Unconventional protein secretion (UPS) mediates protein exocytosis without entering the ER-Golgi secretory route. Here, Wang et al. report SMGL-1 acts as a guanine nucleotide exchange factor for RAB-8 to facilitate apical UPS of integral proteins in Caenorhabditis elegans intestinal epithelia. Unconventional protein secretion (UPS) pathways are conserved across species. However, the underlying mechanisms that regulate Golgi-bypassing UPS of integral proteins remain elusive. In this study, we show that RAB-8 and SMGL-1/NBAS are required for the UPS of integral proteins in C. elegans intestine. SMGL-1 resides in the ER-Golgi intermediate compartment and adjacent RAB-8-positive structures, and NRZ complex component CZW-1/ZW10 is required for this residency. Notably, SMGL-1 acts as a guanine nucleotide exchange factor for RAB-8, ensuring UPS of integral proteins by driving the activation of RAB-8. Furthermore, we show that Pseudomonas aeruginosa infection elevated the expression of SMGL-1 and RAB-8. Loss of SMGL-1 or RAB-8 compromised resistance to environmental colchicine, arsenite, and pathogenic bacteria. These results suggest that the SMGL-1/RAB-8-mediated UPS could integrate environmental signals to serve as a host defense response. Together, by establishing the C. elegans intestine as a multicellular model, our findings provide insights into RAB-8-dependent Golgi-bypassing UPS, especially in the context of epithelia in vivo.
登录
查看更多内容
影响因子：
30.3
作者：
Dierking, Katja;Polanowska, Jolanta;Pujol, Nathalie
通讯作者：
Pujol, Nathalie
影响因子：
3.3
作者：
Gleason AM;Nguyen KC;Hall DH;Grant BD
通讯作者：
Grant BD
SAC-1 通过限制 ARF-6 活性来确保上皮内吞再循环。
DOI：
10.1083/jcb.201711065
发表时间：
2018-06-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen D;Yang C;Liu S;Hang W;Wang X;Chen J;Shi A
通讯作者：
Shi A
影响因子：
11.4
作者：
FULLER, SD;BRAVO, R;SIMONS, K
通讯作者：
SIMONS, K
影响因子：
7.8
作者：
Fourriere, Lou;Kasri, Amal;Miserey-Lenkei, Stephanie
通讯作者：
Miserey-Lenkei, Stephanie