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Publication

Dynamics of mTORC1 activation in response to amino acids.

eLife | 2016

Amino acids are essential activators of mTORC1 via a complex containing RAG GTPases, RAGULATOR and the vacuolar ATPase. Sensing of amino acids causes translocation of mTORC1 to lysosomes, an obligate step for activation. To examine the spatial and temporal dynamics of this translocation, we used live imaging of the mTORC1 component RAPTOR and a cell permeant fluorescent analogue of di-leucine methyl ester. Translocation to lysosomes is a transient event, occurring within 2 min of aa addition and peaking within 5 min. It is temporally coupled with fluorescent leucine appearance in lysosomes and is sustained in comparison to aa stimulation. Sestrin2 and the vacuolar ATPase are negative and positive regulators of mTORC1 activity in our experimental system. Of note, phosphorylation of canonical mTORC1 targets is delayed compared to lysosomal translocation suggesting a dynamic and transient passage of mTORC1 from the lysosomal surface before targetting its substrates elsewhere.

Pubmed ID: 27725083 RIS Download

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Associated grants

Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
Id: BB/K019155/1
Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
Id: BBS/E/B/00001221
Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
Id: BBS/E/B/000C0413
Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
Id: BBS/E/B/000C0417

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