2026-06-14T03:43:06Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/175512024-11-29T18:40:54Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Fawal, Mohamad-Ali
author
Brandt, Marta
author
Djouder, Nabil
funder
Fundación Caja Navarra
funder
Fundación La Caixa
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
2024-02-08T13:25:06Z
2024-02-08T13:25:06Z
2015-04-06
Dev Cell . 2015 Apr 6;33(1):67-81.
10.1016/j.devcel.2015.02.010
1878-1551
Developmental cell
25816988
http://hdl.handle.net/20.500.12105/17551
Ras homolog enriched in brain (Rheb) is critical for mechanistic target of rapamycin complex 1 (mTORC1) activation in response to growth factors and amino acids (AAs). Whereas growth factors inhibit the tuberous sclerosis complex (TSC1-TSC2), a negative Rheb regulator, the role of AAs in Rheb activation remains unknown. Here, we identify microspherule protein 1 (MCRS1) as the essential link between Rheb and mTORC1 activation. MCRS1, in an AA-dependent manner, maintains Rheb at lysosome surfaces, connecting Rheb to mTORC1. MCRS1 suppression in human cancer cells using small interference RNA or mouse embryonic fibroblasts using an inducible-Cre/Lox system reduces mTORC1 activity. MCRS1 depletion promotes Rheb/TSC2 interaction, rendering Rheb inactive and delocalizing it from lysosomes to recycling endocytic vesicles, leading to mTORC1 inactivation. These findings have important implications for signaling mechanisms in various pathologies, including diabetes mellitus and cancer.
eng
MCRS1 binds and couples Rheb to amino acid-dependent mTORC1 activation.
journal article
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URL
https://repisalud.isciii.es/bitstreams/be538864-1283-4138-9908-42ba04c86c42/download
File
MD5
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application/pdf
MCRS1BindsandCouples Rheb_2015.pdf
URL
https://repisalud.isciii.es/bitstreams/5f74f6ea-6a4a-423b-b730-840f8f8243b5/download
File
MD5
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text/plain
MCRS1BindsandCouples Rheb_2015.pdf.txt