Lipid exchange and signaling at ER–Golgi contact sites

Meticulous observations of the cell perinuclear region where the Golgi and the endoplasmic reticulum (ER) networks intermingle have revealed close contact sites of barely 20 nm between these two organelles. Recent studies demonstrate that molecular machineries, including lipid-transfer proteins, enriched in membrane contact sites between ER and trans-Golgi are capable of bridging membranes and exchanging key lipids such as sphingolipid precursors and cholesterol while bypassing the early secretory compartments. This occurs at the cost of an intense phosphoinositide turnover in order to prepare a membrane environment conducive to the signaling and trafficking functions of the trans-Golgi network. A tight control operates in the contact zone to adjust lipid transport and metabolism to the cellular needs.