Rag-Ragulator is the central organizer of the physical architecture of the mTORC1 nutrient-sensing pathway

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00597924" target="_blank" >RIV/61388963:_____/24:00597924 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1073/pnas.2322755121" target="_blank" >https://doi.org/10.1073/pnas.2322755121</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1073/pnas.2322755121" target="_blank" >10.1073/pnas.2322755121</a>

Result language

angličtina

Original language name

Rag-Ragulator is the central organizer of the physical architecture of the mTORC1 nutrient-sensing pathway

Original language description

The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cell growth and metabolism in response to many environmental cues, including nutrients. Amino acids signal to mTORC1 by modulating the guanine nucleotide loading states of the heterodimeric Rag GTPases, which bind and recruit mTORC1 to the lysosomal surface, its site of activation. The Rag GTPases are tethered to the lysosome by the Ragulator complex and regulated by the GATOR1, GATOR2, and KICSTOR multiprotein complexes that localize to the lysosomal surface through an unknown mechanism(s). Here, we show that mTORC1 is completely insensitive to amino acids in cells lacking the Rag GTPases or the Ragulator component p18. Moreover, not only are the Rag GTPases and Ragulator required for amino acids to regulate mTORC1, they are also essential for the lysosomal recruitment of the GATOR1, GATOR2, and KICSTOR complexes, which stably associate and traffic to the lysosome as the GATOR supercomplex. The nucleotide state of RagA/B controls the lysosomal association of GATOR, in a fashion competitively antagonized by the N terminus of the amino acid transporter SLC38A9. Targeting of Ragulator to the surface of mitochondria is sufficient to relocalize the Rags and GATOR to this organelle, but not to enable the nutrient-regulated recruitment of mTORC1 to mitochondria. Thus, our results reveal that the Rag-Ragulator complex is the central organizer of the physical architecture of the mTORC1 nutrient-sensing pathway and underscore that mTORC1 activation requires signal transduction on the lysosomal surface.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Proceedings of the National Academy of Sciences of the United States of America

ISSN

0027-8424

e-ISSN

1091-6490

Volume of the periodical

121

Issue of the periodical within the volume

35

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

e2322755121

UT code for WoS article

001348094500007

EID of the result in the Scopus database

2-s2.0-85201851909