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

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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.