Spatial coupling of mTOR and autophagy augments secretory phenotypes

Masako Narita; Andrew R J Young; Satoko Arakawa; Shamith A Samarajiwa; Takayuki Nakashima; Sei Yoshida; Sungki Hong; Lorraine S Berry; Stefanie Reichelt; Manuela Ferreira; Simon Tavaré; Ken Inoki; Shigeomi Shimizu; Masashi Narita

doi:10.1126/science.1205407

Spatial coupling of mTOR and autophagy augments secretory phenotypes

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

Authors

Masako Narita¹, Andrew R J Young, Satoko Arakawa, Shamith A Samarajiwa, Takayuki Nakashima, Sei Yoshida, Sungki Hong, Lorraine S Berry, Stefanie Reichelt, Manuela Ferreira, Simon Tavaré, Ken Inoki, Shigeomi Shimizu, Masashi Narita

Affiliation

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids / metabolism
Animals
Autophagy*
Cell Line
Cellular Senescence*
Cytoplasm / metabolism
Cytoplasmic Vesicles / metabolism*
Cytoplasmic Vesicles / ultrastructure
Endoplasmic Reticulum, Rough / ultrastructure
Genes, ras
Golgi Apparatus / ultrastructure
HL-60 Cells
Humans
Interleukin-6 / metabolism
Interleukin-8 / metabolism
Lysosomes / metabolism
Lysosomes / ultrastructure
Mice
Monomeric GTP-Binding Proteins / genetics
Monomeric GTP-Binding Proteins / metabolism
Nocodazole / pharmacology
Phagosomes / metabolism
Phagosomes / ultrastructure
Phenotype
Podocytes / metabolism
Podocytes / ultrastructure
Protein Biosynthesis
Proteins / metabolism*
TOR Serine-Threonine Kinases / metabolism*
Vacuoles / ultrastructure
trans-Golgi Network / metabolism
trans-Golgi Network / ultrastructure

Substances

Amino Acids
Interleukin-6
Interleukin-8
Proteins
MTOR protein, human
TOR Serine-Threonine Kinases
RRAGB protein, human
Monomeric GTP-Binding Proteins
Nocodazole

Associated data

GEO/GSE28464

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding