title: Spatial coupling of mTOR and autophagy augments secretory phenotypes.
abstract: 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.
authors.affiliation: Cancer Research UK Cambridge Research Institute (CRI), Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
authors.forename: Masako
authors.initials: M
authors.lastname: Narita
authors.forename: Andrew R J
authors.initials: AR
authors.lastname: Young
authors.forename: Satoko
authors.initials: S
authors.lastname: Arakawa
authors.forename: Shamith A
authors.initials: SA
authors.lastname: Samarajiwa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakashima
authors.forename: Sei
authors.initials: S
authors.lastname: Yoshida
authors.forename: Sungki
authors.initials: S
authors.lastname: Hong
authors.forename: Lorraine S
authors.initials: LS
authors.lastname: Berry
authors.forename: Stefanie
authors.initials: S
authors.lastname: Reichelt
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferreira
authors.forename: Simon
authors.initials: S
authors.lastname: Tavaré
authors.forename: Ken
authors.initials: K
authors.lastname: Inoki
authors.forename: Shigeomi
authors.initials: S
authors.lastname: Shimizu
authors.forename: Masashi
authors.initials: M
authors.lastname: Narita
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D002460:Cell Line; D016922:Cellular Senescence; D003593:Cytoplasm / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D018870:Endoplasmic Reticulum, Rough / Q000648:ultrastructure; D011905:Genes, ras; D006056:Golgi Apparatus / Q000648:ultrastructure; D018922:HL-60 Cells; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D010588:Phagosomes / Q000378:metabolism / Q000648:ultrastructure; D010641:Phenotype; D050199:Podocytes / Q000378:metabolism / Q000648:ultrastructure; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014617:Vacuoles / Q000648:ultrastructure; D021601:trans-Golgi Network / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000596:Amino Acids; D015850:Interleukin-6; D016209:Interleukin-8; D011506:Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C484345:RRAGB protein, human; D020559:Monomeric GTP-Binding Proteins; D015739:Nocodazole