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Mol Biol Cell. 2015 Dec 15;26(25):4686-99. doi: 10.1091/mbc.E15-08-0599. Epub 2015 Oct 21.

CARTS biogenesis requires VAP-lipid transfer protein complexes functioning at the endoplasmic reticulum-Golgi interface.

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School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
Lipid Biology Laboratory, RIKEN, Wako, Saitama 351-0198, Japan.
School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan


Vesicle-associated membrane protein-associated protein (VAP) is an endoplasmic reticulum (ER)-resident integral membrane protein that controls a nonvesicular mode of ceramide and cholesterol transfer from the ER to the Golgi complex by interacting with ceramide transfer protein and oxysterol-binding protein (OSBP), respectively. We report that VAP and its interacting proteins are required for the processing and secretion of pancreatic adenocarcinoma up-regulated factor, whose transport from the trans-Golgi network (TGN) to the cell surface is mediated by transport carriers called "carriers of the trans-Golgi network to the cell surface" (CARTS). In VAP-depleted cells, diacylglycerol level at the TGN was decreased and CARTS formation was impaired. We found that VAP forms a complex with not only OSBP but also Sac1 phosphoinositide phosphatase at specialized ER subdomains that are closely apposed to the trans-Golgi/TGN, most likely reflecting membrane contact sites. Immobilization of ER-Golgi contacts dramatically reduced CARTS production, indicating that association-dissociation dynamics of the two membranes are important. On the basis of these findings, we propose that the ER-Golgi contacts play a pivotal role in lipid metabolism to control the biogenesis of transport carriers from the TGN.

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