Journal Article

Spatial Coupling of mTOR and Autophagy Augments Secretory Phenotypes

Reichelt, Stefanie, Inoki, Ken, Nakashima, Takayuki, Yoshida, Sei, Young, Andrew R. J., Samarajiwa, Shamith A., Arakawa, Satoko, Berry, Lorraine S., Tavaré, Simon, Narita, Masako, Hong, Sungki, Shimizu, Shigeomi, Narita, Masashi, Ferreira, Manuela

2011

Overview

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 occurred 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—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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Amino acids / Amino Acids - metabolism / Animals / Autophagy / Biological and medical sciences / Cell growth / Cell Line / Cell physiology / Cellular / Cellular immunity / Cellular Senescence / Compartments / Cytoplasm - metabolism / Cytoplasmic Vesicles - metabolism / Cytoplasmic Vesicles - ultrastructure / Endoplasmic Reticulum, Rough - ultrastructure / Fluorescent antibody techniques / Fundamental and applied biological sciences. Psychology / Genes, ras / Golgi apparatus / Golgi Apparatus - ultrastructure / guanosine / Guanosines / HL-60 Cells / Humans / Individualized Instruction / Interleukin-6 - metabolism / Interleukin-8 - metabolism / Joining / Kidney cortex / Lysosomes / Lysosomes - metabolism / Lysosomes - ultrastructure / macrophages / mammals / mass / Mice / Molecular and cellular biology / Monomeric GTP-Binding Proteins - genetics / Monomeric GTP-Binding Proteins - metabolism / Nocodazole - pharmacology / Phagosomes - metabolism / Phagosomes - ultrastructure / Phenotype / Phenotypes / Podocytes - metabolism / Podocytes - ultrastructure / Position (location) / Protein Biosynthesis / protein secretion / Protein synthesis / Proteins / Proteins - metabolism / rapamycin / rev genes / Secretion. Exocytosis / Secretions / Synthesis / TOR Serine-Threonine Kinases - metabolism / Trans golgi network / trans-Golgi Network - metabolism / trans-Golgi Network - ultrastructure / Vacuoles - ultrastructure