Spatial Coupling of mTOR and Autophagy Augments Secretory Phenotypes

被引：454

作者：

Narita, Masako ^{[1
]}

Young, Andrew R. J. ^{[1
]}

Arakawa, Satoko ^{[2
]}

Samarajiwa, Shamith A. ^{[1
,3
]}

Nakashima, Takayuki ^{[1
]}

Yoshida, Sei ^{[4
]}

Hong, Sungki ^{[4
]}

Berry, Lorraine S. ^{[1
]}

Reichelt, Stefanie ^{[1
]}

Ferreira, Manuela ^{[1
]}

Tavare, Simon ^{[1
,3
]}

Inoki, Ken ^{[4
]}

Shimizu, Shigeomi ^{[2
]}

Narita, Masashi ^{[1
]}

机构：

[1] Canc Res UK, Cambridge Res Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England

[2] Tokyo Med & Dent Univ, Med Res Inst, Dept Pathol & Cell Biol, Bunkyo Ku, Tokyo 1138510, Japan

[3] Univ Cambridge, Dept Oncol, Cambridge CB2 0RE, England

[4] Univ Michigan, Dept Mol & Integrat Physiol & Internal Med, Inst Life Sci, Ann Arbor, MI 48109 USA

来源：

SCIENCE | 2011年 / 332卷 / 6032期

关键词：

RAG GTPASES; PROTEIN; COMPLEX;

D O I：

10.1126/science.1205407

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：966 / 970

页数：5

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