Elucidation of the mechanism of the retrograde transport from the Golgi apparatus to the endoplasmic reticulum

内质网(ER)的顺行运输被高尔基体的逆行运输所补偿，这两条途径的平衡受到精确的调节。其逆行转运机制尚不清楚。我们鉴定了Synaxin 18(Syn18)，它是一种内质网陷阱，与逆行通路中的膜融合有关。它与其他SNARs(BNIP1、P31和Sec22b)和外周膜蛋白(ZW10、Rint-1和NAG)形成复合体。在本项目中取得了以下成果。(1)NAG分别通过其N-端区和C-端区与P31和ZW10-Rint-1的N-端区相互作用。NAG的作用是调节逆行运输载体与内质网的联系。(2)基因敲除研究表明，p31是细胞存活所必需的。P31基因敲除可诱导内质网应激，导致细胞凋亡。(3)Syn18参与了内质网结构的维持，高尔基体的逆行转运通过未知机制参与了这一功能。(4)Rer1是一种参与维持内质网驻留膜蛋白定位的受体，位于内质网高尔基体中，并参与其在哺乳动物细胞中的组织。

The anterograde transport from the endoplasmic reticulum (ER) is compensated by the retrograde transport from the Golgi apparatus, and a balance of the two pathways is precisely regulated. The mechanism of the retrograde transport remained to be elucidated. We identified syntaxin 18 (Syn18), an ER SNARE implicated in membrane fusion in the retrograde pathway. It forms a complex with other SNAREs (BNIP1, p31, and Sec22b) and peripheral membrane proteins (ZW10, RINT-1, and NAG). The following results have been obtained in this projects. (1) NAG interacts with the N-terminal region of p31 and ZW10-RINT-1 through its N- and C-terminal regions, respectively. NAG functions to mediate the tethering of retrograde transport carriers with the ER. (2) Gene knockout study revealed that p31 is essential for cell viability. Knockout of the p31 gene induces ER stress, leading to apoptosis. (3) Syn18 is involved in the maintenance of the ER structure, and the retrograde transport from the Golgi is related to this function via an unknown mechanism. (4) Rer1, a receptor involved in the maintenance of the localization of ER-resident membrane proteins, is located in the ER-Golgi intermediated compartment and involved in its organization in mammalian cells.