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Ragulator complex protein LAMTOR1

Key component of the Ragulator complex, a multiprotein complex involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids^1,2,3. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane^4,5,6. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated⁷. LAMTOR1 is directly responsible for anchoring the Ragulator complex to the lysosomal membrane⁸. LAMTOR1 wraps around the other subunits of the Ragulator complex to hold them in place and interacts with the Rag GTPases, thereby playing a key role in the recruitment of the mTORC1 complex to lysosomes (By similarity). Also involved in the control of embryonic stem cells differentiation via non-canonical RagC/RRAGC and RagD/RRAGD activation: together with FLCN, it is necessary to recruit and activate RagC/RRAGC and RagD/RRAGD at the lysosomes, and to induce exit of embryonic stem cells from pluripotency via non-canonical, mTOR-independent TFE3 inactivation⁹. Also required for late endosomes/lysosomes biogenesis it may regulate both the recycling of receptors through endosomes and the MAPK signaling pathway through recruitment of some of its components to late endosomes (By similarity). May be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes (By similarity). May also play a role in RHOA activation (By similarity).

AlphaFold DB , UniProt , Accession Q9CQ22, Species MOUSE (Mus musculus, Mouse), Gene Lamtor1, Length 161 aa.