Role of VMP1 in membrane trafficking

Resum

VMP1 is an Endoplasmic Reticulum (ER) multispanning transmembrane protein of unknown function that is highly conserved among metazoan. To shed light on the molecular function of VMP1, we have used mammalian cell culture as cellular model and state of art confocal microscopy techniques as the main experimental approach. In this work, we show that VMP1 accumulates at dynamic ER-subdomains enriched in phospholipid synthesizing enzymes. Interestingly, VMP1 regulates the distribution and dynamics of these enzymes along the ER tubules. Moreover, these subdomains are intimately associated with other organelles such as mitochondria, endosomes, lipid droplets, peroxisomes and autophagosomes, indicating that VMP1 is a new molecular component of multiple ER-Membrane Contact Sites (MCS). Strikingly, MCS between ER and other organelles are enlarged in the absence of VMP1, suggesting that VMP1 regulates the length and function of ER-contact sites rather than acting as a tether. Furthermore, lipid membrane homeostasis of other organelles is compromised after VMP1 depletion, which leads to pleiotropic defects in organelle structure and function. These data strongly suggest that VMP1 function may be essential in maintaining a correct lipid trafficking between phospholipid enriched-ER subdomains and other organelles at MCS by regulating the distribution of the phospholipid synthesizing enzymes along the ER network.