Brecker Margaret, Khakhina Svetlana, Schubert Tyler J, Thompson Zachary, Rubenstein Ronald C
Cystic Fibrosis Center, The Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States.
Front Physiol. 2020 Sep 8;11:574339. doi: 10.3389/fphys.2020.574339. eCollection 2020.
The luminal endoplasmic reticulum (ER) protein of 29 kDa (ERp29) is a ubiquitously expressed cellular agent with multiple critical roles. ERp29 regulates the biosynthesis and trafficking of several transmembrane and secretory proteins, including the cystic fibrosis transmembrane conductance regulator (CFTR), the epithelial sodium channel (ENaC), thyroglobulin, connexin 43 hemichannels, and proinsulin. ERp29 is hypothesized to promote ER to Golgi cargo protein transport COP II machinery through its interactions with the KDEL receptor; this interaction may facilitate the loading of ERp29 clients into COP II vesicles. ERp29 also plays a role in ER stress (ERS) and the unfolded protein response (UPR) and is implicated in oncogenesis. Here, we review the vast array of ERp29's clients, its role as an ER to Golgi escort protein, and further suggest ERp29 as a potential target for therapies related to diseases of protein misfolding and mistrafficking.
29 kDa的内质网腔蛋白（ERp29）是一种广泛表达的细胞因子，具有多种关键作用。ERp29调节几种跨膜蛋白和分泌蛋白的生物合成与运输，包括囊性纤维化跨膜传导调节因子（CFTR）、上皮钠通道（ENaC）、甲状腺球蛋白、连接蛋白43半通道和胰岛素原。据推测，ERp29通过与KDEL受体相互作用促进内质网到高尔基体的货物蛋白运输及COP II机制；这种相互作用可能有助于将ERp29的客户蛋白装载到COP II囊泡中。ERp29在内质网应激（ERS）和未折叠蛋白反应（UPR）中也发挥作用，并与肿瘤发生有关。在这里，我们综述了ERp29的大量客户蛋白、其作为内质网到高尔基体护送蛋白的作用，并进一步提出ERp29作为与蛋白质错误折叠和运输障碍相关疾病治疗的潜在靶点。
