Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

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}

Autophagy-Dependent Production of Secreted Factors Facilitates Oncogenic RAS-Driven Invasion.
R. Lock, C. M. Kenific, A. M. Leidal, E. Salas, and J. Debnath (2014)
Cancer Discovery 4, 466-479
   Abstract »    Full Text »    PDF »
Cellular senescence and its effector programs.
R. Salama, M. Sadaie, M. Hoare, and M. Narita (2014)
Genes & Dev. 28, 99-114
   Abstract »    Full Text »    PDF »
Autophagy and metabolic changes in obesity-related chronic kidney disease.
J. Satriano and K. Sharma (2013)
Nephrol. Dial. Transplant. 28, iv29-iv36
   Abstract »    Full Text »    PDF »
Senescence at a glance.
J. S. Pawlikowski, P. D. Adams, and D. M. Nelson (2013)
J. Cell Sci. 126, 4061-4067
   Abstract »    Full Text »    PDF »
Redistribution of the Lamin B1 genomic binding profile affects rearrangement of heterochromatic domains and SAHF formation during senescence.
M. Sadaie, R. Salama, T. Carroll, K. Tomimatsu, T. Chandra, A. R. J. Young, M. Narita, P. A. Perez-Mancera, D. C. Bennett, H. Chong, et al. (2013)
Genes & Dev. 27, 1800-1808
   Abstract »    Full Text »    PDF »
Comparison of Regulatory T Cells in Hemodialysis Patients and Healthy Controls: Implications for Cell Therapy in Transplantation.
B. Afzali, F. C. Edozie, H. Fazekasova, C. Scotta, P. J. Mitchell, J. B. Canavan, S. Y. Kordasti, P. S. Chana, R. Ellis, G. M. Lord, et al. (2013)
Clin. J. Am. Soc. Nephrol. 8, 1396-1405
   Abstract »    Full Text »    PDF »
Radioresistant Cancer Cells Can Be Conditioned to Enter Senescence by mTOR Inhibition.
H. Y. Nam, M. W. Han, H. W. Chang, Y. S. Lee, M. Lee, H. J. Lee, B. W. Lee, H. J. Lee, K. E. Lee, M. K. Jung, et al. (2013)
Cancer Res. 73, 4267-4277
   Abstract »    Full Text »    PDF »
Lysosome-mediated processing of chromatin in senescence.
A. Ivanov, J. Pawlikowski, I. Manoharan, J. van Tuyn, D. M. Nelson, T. S. Rai, P. P. Shah, G. Hewitt, V. I. Korolchuk, J. F. Passos, et al. (2013)
J. Cell Biol. 202, 129-143
   Abstract »    Full Text »    PDF »
Rheb/mTORC1 Signaling Promotes Kidney Fibroblast Activation and Fibrosis.
L. Jiang, L. Xu, J. Mao, J. Li, L. Fang, Y. Zhou, W. Liu, W. He, A. Z. Zhao, J. Yang, et al. (2013)
J. Am. Soc. Nephrol. 24, 1114-1126
   Abstract »    Full Text »    PDF »
Suppression of Autophagy in Osteocytes Mimics Skeletal Aging.
M. Onal, M. Piemontese, J. Xiong, Y. Wang, L. Han, S. Ye, M. Komatsu, M. Selig, R. S. Weinstein, H. Zhao, et al. (2013)
J. Biol. Chem. 288, 17432-17440
   Abstract »    Full Text »    PDF »
Constitutive HER2 Signaling Promotes Breast Cancer Metastasis through Cellular Senescence.
P. D. Angelini, M. F. Z. Fluck, K. Pedersen, J. L. Parra-Palau, M. Guiu, C. Bernado Morales, R. Vicario, A. Luque-Garcia, N. P. Navalpotro, J. Giralt, et al. (2013)
Cancer Res. 73, 450-458
   Abstract »    Full Text »    PDF »
Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation.
E. F. Castillo, A. Dekonenko, J. Arko-Mensah, M. A. Mandell, N. Dupont, S. Jiang, M. Delgado-Vargas, G. S. Timmins, D. Bhattacharya, H. Yang, et al. (2012)
PNAS 109, E3168-E3176
   Abstract »    Full Text »    PDF »
Wnt Antagonist SFRP1 Functions as a Secreted Mediator of Senescence.
D. J. Elzi, M. Song, K. Hakala, S. T. Weintraub, and Y. Shiio (2012)
Mol. Cell. Biol. 32, 4388-4399
   Abstract »    Full Text »    PDF »
Hepatitis C Virus Upregulates Beclin1 for Induction of Autophagy and Activates mTOR Signaling.
S. Shrivastava, J. Bhanja Chowdhury, R. Steele, R. Ray, and R. B. Ray (2012)
J. Virol. 86, 8705-8712
   Abstract »    Full Text »    PDF »
Mammalian target of rapamycin and the kidney. I. The signaling pathway.
W. Lieberthal and J. S. Levine (2012)
Am J Physiol Renal Physiol 303, F1-F10
   Abstract »    Full Text »    PDF »
Autophagy and cell growth - the yin and yang of nutrient responses.
T. P. Neufeld (2012)
J. Cell Sci. 125, 2359-2368
   Abstract »    Full Text »    PDF »
Inhibition of MTOR Disrupts Autophagic Flux in Podocytes.
D. P. Cina, T. Onay, A. Paltoo, C. Li, Y. Maezawa, J. De Arteaga, A. Jurisicova, and S. E. Quaggin (2012)
J. Am. Soc. Nephrol. 23, 412-420
   Abstract »    Full Text »    PDF »
Regulation of TOR by small GTPases.
R. V. Duran and M. N. Hall (2012)
EMBO Rep. 13, 121-128
   Abstract »    Full Text »    PDF »
Autophagy and Cancer.
L. Y. Mah and K. M. Ryan (2012)
Cold Spring Harb Perspect Biol 4, a008821
   Abstract »    Full Text »    PDF »
The dynamic nature of autophagy in cancer.
A. C. Kimmelman (2011)
Genes & Dev. 25, 1999-2010
   Abstract »    Full Text »    PDF »
Regulation of TFEB and V-ATPases by mTORC1.
S. Pena-Llopis, S. Vega-Rubin-de-Celis, J. C. Schwartz, N. C. Wolff, T. A. T. Tran, L. Zou, X.-J. Xie, D. R. Corey, and J. Brugarolas (2011)
EMBO J. 30, 3242-3258
   Abstract »    Full Text »    PDF »
The TASCC of Secretion.
R. Zoncu and D. M. Sabatini (2011)
Science 332, 923-925
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882