Department of Biomolecular Science, Faculty of Engineering, Gifu University, Gifu, Japan.
FEBS Lett. 2011 Aug 4;585(15):2481-7. doi: 10.1016/j.febslet.2011.06.029. Epub 2011 Jun 30.
In this study, we found that Cysteine-rich with EGF-like domains 2 (CRELD2), a novel endoplasmic reticulum stress-inducible protein, is not only localized in the ER-Golgi apparatus but also spontaneously secreted. Deletion of four C-terminal amino acids from mouse CRELD2 or addition of tag-peptides to its C-terminus dramatically enhanced CRELD2 secretion. Intra- and extra-cellular CRELD2 is differentially glycosylated and its spontaneous secretion was significantly prevented by overexpression of a dominant negative mutant Sar1 and treatment with brefeldin A. Overexpression of wild-type GRP78 remarkably enhanced the secretion of wild-type but not mutant CRELD2. Our results demonstrate both that CRELD2 is a novel secretory glycoprotein regulated by Sar1 and GRP78 and that the C-terminal of CRELD2 plays a crucial role in its secretion.
在这项研究中，我们发现富含半胱氨酸的表皮生长因子样域蛋白 2（CRELD2），一种新的内质网应激诱导蛋白，不仅定位于内质网-高尔基体装置，而且还自发分泌。从小鼠 CRELD2 中删除四个 C 末端氨基酸或在其 C 末端添加标记肽，可显著增强 CRELD2 的分泌。细胞内和细胞外的 CRELD2 存在差异糖基化，其自发分泌可被过表达显性负性突变 Sar1 和布雷菲德菌素 A 处理显著抑制。野生型 GRP78 的过表达显著增强了野生型 CRELD2 的分泌，但突变型 CRELD2 的分泌则没有增强。我们的结果表明，CRELD2 是一种受 Sar1 和 GRP78 调控的新型分泌糖蛋白，CRELD2 的 C 末端在其分泌中起着关键作用。
