2015
DOI: 10.1083/jcb.201504097
|View full text |Cite
|
Sign up to set email alerts
|

Abstract: The rapid activation of the mechanistic target of rapamycin complex-1 (mTORC1) by growth factors is increased by extracellular amino acids through yet-undefined mechanisms of amino acid transfer into endolysosomes. Because the endocytic process of macropinocytosis concentrates extracellular solutes into endolysosomes and is increased in cells stimulated by growth factors or tumor-promoting phorbol esters, we analyzed its role in amino acid–dependent activation of mTORC1. Here, we show that growth factor-depend… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

10
108
0

Year Published

2016
2016
2023
2023

Publication Types

Select...
5
2
1

Relationship

2
6

Authors

Journals

citations
Cited by 86 publications
(118 citation statements)
references
References 65 publications
(102 reference statements)
10
108
0
Order By: Relevance
“…1C). It was shown previously that inhibition of PDGF-induced macropinocytosis by J/B blocked mTORC1 activation, as measured by S6K phosphorylation (Yoshida et al, 2015b). Likewise, nocodazole blocked PDGF-induced S6K phosphorylation ( Fig.…”
Section: Nocodazole Blocks Pdgf-induced Macropinocytosis and Mtorc1 Asupporting
confidence: 64%
See 2 more Smart Citations
“…1C). It was shown previously that inhibition of PDGF-induced macropinocytosis by J/B blocked mTORC1 activation, as measured by S6K phosphorylation (Yoshida et al, 2015b). Likewise, nocodazole blocked PDGF-induced S6K phosphorylation ( Fig.…”
Section: Nocodazole Blocks Pdgf-induced Macropinocytosis and Mtorc1 Asupporting
confidence: 64%
“…mTORC1 is activated at lysosomal membranes by two small GTPases, Rag and Rheb (Saito et al, 2005, Sancak et al, 2010, Betz and Hall, 2013, Saxton and Sabatini, 2017. Macropinosomes induced by receptor activation deliver extracellular nutrients into lysosomes, where lysosome-associated membrane protein complexes detect the increased luminal concentrations of amino acids and trigger the activation of Rag GTPases (Yoshida et al, 2015b, Yoshida et al, 2018, Zoncu et al, 2011. Activated Rag recruits mTORC1 from cytosol to lysosomes (Sancak et al, 2008, Sancak et al, 2010.…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…A faster way than autophagy induction to reactivate mTORC1 in leucine-starved cells is to feed them extracellular proteins, such as albumin, which are engulfed via macropinocytosis and degraded into amino acids in lysosomes for use in growth-promoting processes (Palm et al, 2015; Yoshida et al, 2015). In leucine-starved HEK-293T cells, which do not have high levels of macropinocytosis (Wang et al, 2014), the addition of 3% albumin to the medium took about 4 hours to moderately restore mTORC1 signaling, an effect that depended on SLC38A9 (Figure S7A).…”
Section: Resultsmentioning
confidence: 99%
“…A constant flow of prey-derived solutes from these degradative organelles through transporters into the cytosol is maintained during the growth of such phagotrophic cells as long as feeding can continue. Metazoan cells appear to retain a version of this ancient system (Goberdhan et al, 2005;Nicklin et al, 2009;Wang et al, 2015;Rebsamen et al, 2015), and it has been recently shown that delivery of amino acids to lysosomes is required for fast activation of TORC1 in response to platelet-derived growth factor and macrophage colony-stimulating factor, with a parallel cytosolic signal through the Akt protein kinase also being necessary (Yoshida et al, 2015). Growth factors stimulate anabolic metabolism, but their efficiency in doing so is modulated by the supply of amino acids available from macroautophagy and other cell-autonomous sources, as well as by nutrients delivered from the vasculature.…”
Section: Macropinocytosis In Life and Death -Roles For Rasmentioning
confidence: 99%