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mTORC1 Activation Requires DRAM-1 by Facilitating Lysosomal Amino Acid Efflux.

Florian Beaumatin | Jim O'Prey | Valentin J A Barthet | Barbara Zunino | Jean-Philippe Parvy | Alexis Maximilien Bachmann | Margaret O'Prey | Elżbieta Kania | Pablo Sierra Gonzalez | Robin Macintosh | Laurence Y Lao | Colin Nixon | Jonathan Lopez | Jaclyn S Long | Stephen W G Tait | Kevin M Ryan
Molecular cell | 2019

Sensing nutrient availability is essential for appropriate cellular growth, and mTORC1 is a major regulator of this process. Mechanisms causing mTORC1 activation are, however, complex and diverse. We report here an additional important step in the activation of mTORC1, which regulates the efflux of amino acids from lysosomes into the cytoplasm. This process requires DRAM-1, which binds the membrane carrier protein SCAMP3 and the amino acid transporters SLC1A5 and LAT1, directing them to lysosomes and permitting efficient mTORC1 activation. Consequently, we show that loss of DRAM-1 also impacts pathways regulated by mTORC1, including insulin signaling, glycemic balance, and adipocyte differentiation. Interestingly, although DRAM-1 can promote autophagy, this effect on mTORC1 is autophagy independent, and autophagy only becomes important for mTORC1 activation when DRAM-1 is deleted. These findings provide important insights into mTORC1 activation and highlight the importance of DRAM-1 in growth control, metabolic homeostasis, and differentiation.

Pubmed ID: 31492633

Antibodies used in this publication

Associated grants

  • Agency: Worldwide Cancer Research, United Kingdom
    Id: 16-1194

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

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