Recombinant Human Ragulator complex protein LAMTOR1 (LAMTOR1)

Function

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 (PubMed:20381137, PubMed:22980980, PubMed:29158492). 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 (PubMed:22053050, PubMed:22980980, PubMed:28935770, PubMed:29158492, PubMed:30181260, PubMed:31001086, PubMed:32686708, PubMed:36476874). Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated (PubMed:20381137, PubMed:22980980, PubMed:29158492). LAMTOR1 is directly responsible for anchoring the Ragulator complex to the lysosomal membrane (PubMed:31001086, PubMed:32686708). 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 (PubMed:28935770, PubMed:29107538, PubMed:29123114, PubMed:29285400). 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 inactivation (By similarity). 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 (PubMed:20381137, PubMed:22980980). May be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes (PubMed:20544018). May also play a role in RHOA activation (PubMed:19654316)

Subcellular Location

Lysosome membrane (Lipid-anchor); Late endosome membrane (Lipid-anchor)

Subunit

Part of the Ragulator complex composed of LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5 (PubMed:20381137, PubMed:22980980, PubMed:28935770, PubMed:29107538, PubMed:29123114, PubMed:29158492, PubMed:29285400, PubMed:31601708, PubMed:32868926, PubMed:35338845, PubMed:36103527, PubMed:36697823). LAMTOR4 and LAMTOR5 form a heterodimer that interacts, through LAMTOR1, with a LAMTOR2, LAMTOR3 heterodimer (PubMed:20381137, PubMed:22980980). Interacts with LAMTOR2 and LAMTOR3; the interaction is direct (PubMed:20381137, PubMed:22980980). The Ragulator complex interacts with both the mTORC1 complex and heterodimers constituted of the Rag GTPases RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and RagD/RRAGD; regulated by amino acid availability (PubMed:20381137, PubMed:22980980, PubMed:32868926). The Ragulator complex interacts with SLC38A9; the probable amino acid sensor (PubMed:22980980, PubMed:25561175, PubMed:25567906). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator (PubMed:31672913, PubMed:31704029). Associates with the lysosomal V-ATPase complex; interaction promotes the guanine nucleotide exchange factor (GEF) of the Ragulator complex (PubMed:36476874). Interacts with MMP14 (PubMed:19654316). Interacts with CDKN1B; prevents the interaction of CDKN1B with RHOA leaving RHOA in a form accessible to activation by ARHGEF2 (PubMed:19654316). Interacts with PIP4P1 (PubMed:29644770)

• Wan D. et al. Large-scale cDNA transfection screening for genes related to cancer development and progression. — Proc. Natl. Acad. Sci. U.S.A. (2004)
• Ebert L. et al. Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201). (JUN-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Bienvenut W.V. et al. PubMed: CI-590RJT58FU1V (JUN-)
• Beausoleil S.A. et al. A probability-based approach for high-throughput protein phosphorylation analysis and site localization. — Nat. Biotechnol. (2006)
• Dephoure N. et al. A quantitative atlas of mitotic phosphorylation. — Proc. Natl. Acad. Sci. U.S.A. (2008)
• Gauci S. et al. Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. — Anal. Chem. (2009)