Seminar by Thierry Galli, 10th October 2023, Salle des Thèses 3rd Floor.
Topic: Molecular and cellular mechanisms of late endosomal autophagic secretion and its role in cell-cell communication
Abstract: VAMP7, a tetanus neurotoxin insensitive vesicular SNARE has been shown to be involved in autophagy, exocytosis, and the lysosomal secretion of ATP. We have recently characterized a late endosomal/amphisomal secretion mediated by VAMP7 involved in the secretion of endoplasmic reticulum (ER) proteins such as RTN3. This VAMP7-dependent secretion was boosted upon the inhibition of degradative autophagy. Here we present our results pertaining to the characterization of this novel unconventional secretory pathway. We first establish that VAMP7-dependent secretion is conserved in cells of non-neuronal origins. Indeed, like in PC12 cells, the secretion of the short form of RTN3 is decreased in VAMP7- and increased in ATG5-KO epithelial NRK and glioma RG2 cells. We further show that apart from the secretion of ER proteins, VAMP7-dependent secretion is also responsible for the secretion of mitochondrial proteins. In addition, in the absence of VAMP7, mitochondrial health is impaired in the form of reduced mitochondrial respiration, and increased mitochondrial number and length. Owing to the structural and functional links between ER and mitochondria, we propose that the VAMP7-dependent secretion is important for maintaining organellar health and function by allowing for removal of ER and mitochondrial elements through late endosomal autophagic secretion. We also show that the media conditioned by the VAMP7 and ATG5KO cells have a significant effect on the glioma cell phenotype thus suggesting a potential function of late endosomal autophagic secretion in cancer.