Spatial Coupling of mTOR and Autophagy Augments Secretory Phenotypes

Protein synthesis and autophagic degradation are regulated in an opposite manner by mammalian target of rapamycin (mTOR), whereas under certain conditions it would be beneficial if they occured in unison to handle rapid protein turnover. We observed a distinct cellular compartment at the trans-side of the Golgi apparatus, the ‘TOR-autophagy spatial coupling compartment’ (TASCC), where (auto)lysosomes and mTOR accumulated during Ras-induced senescence. mTOR recruitment to the TASCC was amino acid- and Rag guanosine triphosphatase (GTPase)-dependent, and disruption of mTOR localization to the TASCC suppressed interleukin-6/8 synthesis. TASCC-formation was observed during macrophage differentiation and in glomerular podocytes; both displayed increased protein secretion. The spatial coupling of cells’ catabolic and anabolic machinery could augment their respective functions and facilitate the mass synthesis of secretory proteins. To compare gene expression profile between growing and oncogenic Ras induced senescence, 4OHT inducible ER:H-RasV12 was stably expressed in IMR90 human diploid fibroblasts. Total RNA was isolated from day 0 and day 4 after 4OHT addition. There were 3 biological replicates for each of day0 and day 4 timepoints.