Publication Date:
2011-04-23
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426290/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426290/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Narita, Masako -- Young, Andrew R J -- Arakawa, Satoko -- Samarajiwa, Shamith A -- Nakashima, Takayuki -- Yoshida, Sei -- Hong, Sungki -- Berry, Lorraine S -- Reichelt, Stefanie -- Ferreira, Manuela -- Tavare, Simon -- Inoki, Ken -- Shimizu, Shigeomi -- Narita, Masashi -- DK083491/DK/NIDDK NIH HHS/ -- R01 DK083491/DK/NIDDK NIH HHS/ -- R01 DK083491-03/DK/NIDDK NIH HHS/ -- Cancer Research UK/United Kingdom -- New York, N.Y. -- Science. 2011 May 20;332(6032):966-70. doi: 10.1126/science.1205407. Epub 2011 Apr 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK Cambridge Research Institute (CRI), Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21512002" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acids/metabolism
;
Animals
;
*Autophagy
;
*Cell Aging
;
Cell Line
;
Cytoplasm/metabolism
;
Cytoplasmic Vesicles/*metabolism/ultrastructure
;
Endoplasmic Reticulum, Rough/ultrastructure
;
Genes, ras
;
Golgi Apparatus/ultrastructure
;
HL-60 Cells
;
Humans
;
Interleukin-6/metabolism
;
Interleukin-8/metabolism
;
Lysosomes/metabolism/ultrastructure
;
Mice
;
Monomeric GTP-Binding Proteins/genetics/metabolism
;
Nocodazole/pharmacology
;
Phagosomes/metabolism/ultrastructure
;
Phenotype
;
Podocytes/metabolism/ultrastructure
;
Protein Biosynthesis
;
Proteins/*secretion
;
TOR Serine-Threonine Kinases/*metabolism
;
Vacuoles/ultrastructure
;
trans-Golgi Network/metabolism/ultrastructure
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
