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Science 332 (6032): 966-970

Copyright © 2011 by the American Association for the Advancement of Science

Spatial Coupling of mTOR and Autophagy Augments Secretory Phenotypes

Masako Narita,1,* Andrew R. J. Young,1,* Satoko Arakawa,2 Shamith A. Samarajiwa,1,3 Takayuki Nakashima,1,{dagger} Sei Yoshida,4 Sungki Hong,4 Lorraine S. Berry,1 Stefanie Reichelt,1 Manuela Ferreira,1,{ddagger} Simon Tavaré,1,3 Ken Inoki,4 Shigeomi Shimizu,2 Masashi Narita1,§

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.

1 Cancer Research UK Cambridge Research Institute (CRI), Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
2 Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
3 Department of Oncology, University of Cambridge, Cambridge CB2 0RE, UK.
4 Life Sciences Institute, Department of Molecular and Integrative Physiology and Internal Medicine, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109, USA.

* These authors contributed equally to this work.

{dagger} Present address: Kyowa Hakko Kirin, Shizuoka 411-8731, Japan.

{ddagger} Present address: Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, 1649-028 Lisbon, Portugal.

§ To whom correspondence should be addressed. E-mail: masashi.narita{at}cancer.org.uk


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