Illuminating the membrane contact sites between the endoplasmic reticulum and the trans-Golgi network

Membrane contact sites (MCSs) between different organelles have been identified and extensively studied over the last decade. Several classes of MCSs have now well-established roles, although the contacts between the endoplasmic reticulum (ER) and the trans-side of the Golgi network (TGN) have long remained elusive. Until recently, the study of ER-TGN contact sites has represented a major challenge in the field, as a result of the lack of suitable visualization and isolation techniques. Only in the last 5 years has the combination of advanced technologies and innovative approaches permitted the identification of new molecular players and the functions of ER-TGN MCSs that couple lipid metabolism and anterograde transport. Although much has yet to be discovered, it is now established that ER-TGN MCSs control phosphatidyl-4-phosphate homeostasis by coupling the cis and the trans activity of the ER-resident 4-phosphatase Sac1. In this review, we focus on recent advances on the composition and function of ER-TGN MCSs.