ENDOMEMBRANE PROTEIN 70 (EMP70) proteins constitute a 12-member superfamily in Arabidopsis thaliana, and are the most abundant protein species in plant Golgi proteomes. However, the physiological functions of EMPs in plants remain largely unknown. Here we have demonstrated that two AtEMP12 T-DNA insertion mutants are sensitive to ER (endoplasmic reticulum) stress as induced by tunicamycin and dithiothreitol treatments. Interestingly, the unfolded protein response (UPR) is constitutively activated in the knockout mutant emp12-1 under normal growth conditions, suggesting that the activation is a result of insufficient chaperones in the ER to aid protein folding. Indeed, we have further shown that BiP is secreted into the apoplast in emp12-1, while the K/HDEL receptor ERD2a, which regulates BiP trafficking, is exclusively localized in the ER in emp12-1, instead of its known ER-Golgi dual-localization. Given an enhanced retrograde transport of ERD2a, along with less dimerized receptor formed in the absence of EMP12, ERD2a may be prematurely returned to the ER without its bound ligands. Therefore, we propose that EMP12 may act as a novel regulator of the K/HDEL receptor to ensure an effective retrograde transport of K/HDEL ligands.

内膜蛋白70（EMP70）蛋白在拟南芥中构成12个成员的超家族，是植物高尔基体蛋白组中最丰富的蛋白种类。但是，植物中EMPs的生理功能仍然未知。在这里，我们证明了两个AtEMP12 T-DNA插入突变体对衣霉素和二硫苏糖醇治疗诱导的ER（内质网）胁迫敏感。有趣的是，在正常生长条件下，敲除突变体emp12-1中的未折叠蛋白应答（UPR）被组成性激活，这表明该激活是由于ER中伴侣分子不足以帮助蛋白质折叠的结果。实际上，我们进一步表明，在emp12-1中，BiP分泌到了质外体中，而K / HDEL受体ERD2a调节了BiP的运输，仅在emp12-1中位于ER中，而不是其已知的ER-Golgi双重定位。考虑到ERD2a逆行转运的增强，以及在没有EMP12的情况下形成的二聚体受体减少，ERD2a可能会过早返回到ER，而没有结合的配体。因此，我们建议EMP12可以充当K / HDEL受体的新型调节剂，以确保K / HDEL配体的有效逆行转运。