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Science. 2011 May 20;332(6032):966-70. doi: 10.1126/science.1205407. Epub 2011 Apr 21.

Spatial coupling of mTOR and autophagy augments secretory phenotypes.

Author information

1
Cancer Research UK Cambridge Research Institute (CRI), Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.

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.

Comment in

PMID:
21512002
PMCID:
PMC3426290
DOI:
10.1126/science.1205407
[Indexed for MEDLINE]
Free PMC Article

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