DRAM-1 is required for mTORC1 activation by facilitating lysosomal amino acid efflux

Beaumatin, F. et al. (2019) DRAM-1 is required for mTORC1 activation by facilitating lysosomal amino acid efflux. Molecular Cell, (doi:10.1016/j.molcel.2019.07.021) (PMID:31492633) (Early Online Publication)

Beaumatin, F. et al. (2019) DRAM-1 is required for mTORC1 activation by facilitating lysosomal amino acid efflux. Molecular Cell, (doi:10.1016/j.molcel.2019.07.021) (PMID:31492633) (Early Online Publication)

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Abstract

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.

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:O'Prey, Mr James and Nixon, Mr Colin and Long, Dr Jaclyn and Barthet, Valentin and Tait, Professor Stephen and O'Prey, Mrs Margaret and Lopez, Dr Jonathan and Beaumatin, Dr Florian and Parvy, Dr Jean-Philippe and Ryan, Professor Kevin
Authors: Beaumatin, F., O'Prey, J., Barthet, V. J.A., Zunino, B., Parvy, J.-P., Bachmann, A. M., O'Prey, M., Kania, E., Gonzalez, P. S., Macintosh, R., Lao, L. Y., Nixon, C., Lopez, J., Long, J. S., Tait, S. W.G., and Ryan, K. N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Molecular Cell
Publisher:Elsevier
ISSN:1097-2765
ISSN (Online):1097-4164
Published Online:03 September 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Molecular Cell 2019
Publisher Policy:Reproduced under a Creative Commons License

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