Activation of mTORC1[edit]

The lysosomal membrane is the main area to which the mTORC1 is activation. However, some activation can occur in the Golgi apparatus and the peroxisome^[1]. In mammalian cells, GTPase RagA and RagB are heterodimers with RagC or RagD respectively. When amino acids are present RagA/B GTPase becomes activated which leads to the translocation of mTORC1 via the Raptor in the cytoplasm, to the lysosome. This brings mTORC1 in closer proximity to Rheb. Rheb can either cause a conformational change in the mTORC1 which leads to increase substrate turnover or it can induce kinase activity of the mTORC1. Rags do not contain membrane-targeting sequences and as a result depend on the Ragulator complex to bind to the lysosome.^[2]

Unlike other amino acids that indirectly activate mTORC1, Leucine, an amino acid has a unique capability. It has the ability to directly activate mTORC1 in cells that are starved of amino acids. LRS (leucyltRNA synthetase) found in yeast is a molecule that can interact with Rags directly activating the molecule.^[2]

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^ Yao, Yao; Jones, Edith; Inoki, Ken (2017-07-07). "Lysosomal Regulation of mTORC1 by Amino Acids in Mammalian Cells". Biomolecules. 7 (3). doi:10.3390/biom7030051. ISSN 2218-273X. PMC 5618232. PMID 28686218.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
^ ^a ^b Groenewoud, Marlous J.; Zwartkruis, Fried J. T. (2013-8). "Rheb and Rags come together at the lysosome to activate mTORC1". Biochemical Society Transactions. 41 (4): 951–955. doi:10.1042/BST20130037. ISSN 1470-8752. PMID 23863162. {{cite journal}}: Check date values in: |date= (help)

[1] Yao, Yao; Jones, Edith; Inoki, Ken (2017-07-07). "Lysosomal Regulation of mTORC1 by Amino Acids in Mammalian Cells". Biomolecules. 7 (3). doi:10.3390/biom7030051. ISSN 2218-273X. PMC 5618232. PMID 28686218.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)

[:0-2] Groenewoud, Marlous J.; Zwartkruis, Fried J. T. (2013-8). "Rheb and Rags come together at the lysosome to activate mTORC1". Biochemical Society Transactions. 41 (4): 951–955. doi:10.1042/BST20130037. ISSN 1470-8752. PMID 23863162. {{cite journal}}: Check date values in: |date= (help)

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