Affinage

LAMTOR1

Ragulator complex protein LAMTOR1 · UniProt Q6IAA8

Length
161 aa
Mass
17.7 kDa
Annotated
2026-06-10
35 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LAMTOR1 is a lysosomal membrane anchor that scaffolds the pentameric Ragulator complex on the surface of late endosomes/lysosomes, where it integrates amino acid signals through interaction with the v-ATPase to recruit and activate mTORC1, while also routing a branch of MAPK signaling (PMID:24377928). Its lysosomal positioning and stability depend on N-terminal lipid modifications: NMT1 myristoylates Gly2 to stabilize the protein and direct it to lysosomes (PMID:34999170), and palmitoylation—including ZDHHC9-mediated modification at Cys3/Cys4—is rapidly induced ahead of amino-acid-driven mTORC1 activation and is required for mTORC1 recruitment (PMID:31001086, PMID:41856969). LAMTOR1 function is further tuned by ubiquitination: TRAF4 catalyzes amino-acid-dependent K63-linked polyubiquitination at K151 to promote Rag GTPase binding and mTORC1 activation (PMID:38229144), USP32 deubiquitinates LAMTOR1 to preserve its v-ATPase interaction and Ragulator activity (PMID:36476874), and UBE3A-mediated ubiquitination targets it for proteasomal degradation (PMID:30020076). Through this mTORC1 hub, LAMTOR1 governs autophagy and the lysosomal biogenesis program via TFEB (PMID:29686050, PMID:39424220), and controls diverse cell-fate and physiological outputs including macrophage M2 polarization (PMID:27731330), T cell function and immune tolerance (PMID:28768723), intestinal goblet cell differentiation (PMID:32641600), and epidermal lysosome-dependent catabolism required for skin barrier formation (PMID:23781028). Independently of mTORC1, LAMTOR1 directly binds and tonically inhibits the lysosomal Ca2+ channel TRPML1 through its N-terminal domain, thereby controlling dynein-driven dendritic lysosome trafficking, synaptic plasticity, and learning (PMID:35099830, PMID:39650798). Aberrant elevation of LAMTOR1-driven mTORC1 signaling contributes to the neuronal dysfunction of Angelman syndrome, where loss of UBE3A stabilizes LAMTOR1 and hyperactivates mTORC1 in hippocampal neurons (PMID:30020076).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2010 Medium

    Before its signaling role was defined, LAMTOR1 was placed at the late endosome/lysosome surface and linked to a discrete cellular process—cholesterol homeostasis—establishing it as a lipid-anchored membrane protein with functional consequences for cargo trafficking.

    Evidence siRNA knockdown, overexpression, cholesterol assays and detergent-resistant membrane proteomics in cultured cells

    PMID:20544018

    Open questions at the time
    • Did not connect cholesterol phenotype to a defined molecular complex or signaling pathway
    • Mechanism linking the lysosomal anchor to cholesterol egress unresolved
  2. 2010 Medium

    A parallel line established a cytoplasmic-facing function in cell motility, showing LAMTOR1 activates RhoA/RhoC to drive metastasis, indicating roles beyond a passive membrane anchor.

    Evidence shRNA knockdown, mouse tail-vein metastasis assay, Rho activation assays in melanoma cells

    PMID:21087931

    Open questions at the time
    • Relationship between Rho activation and the lysosomal Ragulator function not reconciled
    • Direct biochemical link to Rho GTPases not structurally defined
  3. 2012 Medium

    Loss-of-function work showed LAMTOR1 restrains autophagic flux and lysosomal-driven cell death, revealing an mTORC1-independent branch in which its depletion triggers ROS-dependent p53 activation.

    Evidence siRNA knockdown, ROS and apoptosis assays, autophagic flux and p53 pathway analysis

    PMID:22513874

    Open questions at the time
    • Mechanism coupling lysosomal scattering to ROS production unclear
    • Did not distinguish scaffold loss from broader lysosome dysfunction
  4. 2013 High

    In vivo conditional ablation in epidermis tied LAMTOR1 to lysosome maturation and lysosome–autophagosome coupling required for tissue development, moving the gene from cell-line phenotypes to an organismal developmental role.

    Evidence Epidermis-specific conditional knockout mouse, electron microscopy, lysosome behavior assays

    PMID:23781028

    Open questions at the time
    • Did not separate mTORC1-dependent from mTORC1-independent contributions to the barrier defect
  5. 2014 High

    The integrated biochemical model was consolidated: LAMTOR1 is the lipid-anchored scaffold of the pentameric Ragulator that engages Rag GTPases and v-ATPase to activate mTORC1 and recruits MEK1 via MP1/LAMTOR3 for MAPK signaling.

    Evidence Biochemical fractionation, reciprocal co-immunoprecipitation, membrane localization assays synthesizing multi-lab work

    PMID:24377928

    Open questions at the time
    • Stoichiometry of v-ATPase engagement during amino acid sensing not fully resolved
    • Structural basis of LAMTOR1 anchoring not described here
  6. 2015 Medium

    Mechanistic dissection showed LAMTOR1 loss promotes starvation survival via p27kip1, identifying a specific effector linking the scaffold to autophagy regulation.

    Evidence p18 knockout MEFs, LC3-II immunoblot, p27kip1 phosphorylation analysis and epistasis by p27kip1 knockdown

    PMID:26032166

    Open questions at the time
    • How LAMTOR1 controls p27kip1 phosphorylation biochemically unresolved
    • Relationship to mTORC1-dependent autophagy control not delineated
  7. 2016 High

    Myeloid-specific genetics established LAMTOR1 as the amino-acid-sensing scaffold required for M2 macrophage polarization and identified LXR/25-hydroxycholesterol as downstream effectors, translating the molecular hub into immune cell fate.

    Evidence Myeloid conditional knockout, polarization assays, v-ATPase/mTOR pharmacology, 25-HC measurements

    PMID:27731330

    Open questions at the time
    • How mTORC1 output specifies M2 over M1 transcriptionally not fully mapped
  8. 2017 High

    T cell and Treg conditional knockouts demonstrated LAMTOR1 is essential for mTORC1-dependent T cell proliferation, Th17 polarization, and regulatory T cell suppressive function, with loss causing autoimmunity.

    Evidence T-cell- and Foxp3-specific conditional KO mice, polarization/proliferation assays, mTORC1 readouts, EAE model

    PMID:28768723

    Open questions at the time
    • Selective dependence of Th17 (but not Th1/Th2) on LAMTOR1 mechanistically unexplained
  9. 2018 High

    Two studies placed LAMTOR1 upstream of TFEB and revealed disease-relevant regulation: LAMTOR1/mTORC1 controls TFEB phosphorylation in innate immunity, and UBE3A-mediated degradation of LAMTOR1 links its stability to Angelman syndrome neuronal pathology.

    Evidence Myeloid conditional KO with TFEB localization and LPS/bleomycin challenge; co-IP, ubiquitination assays, in vivo knockdown rescue, LTP and behavior in an Angelman model

    PMID:29686050 PMID:30020076

    Open questions at the time
    • UBE3A ubiquitination site on LAMTOR1 not mapped
    • How TFEB control integrates with other LAMTOR1 outputs not unified
  10. 2019 Medium

    The lipid-modification logic and additional functional contexts were expanded: palmitoylation of LAMTOR1 was shown to be dynamic and instructive for mTORC1 activation, and LAMTOR1 was implicated in xenophagy and pancreatic β-cell insulin secretion.

    Evidence Acyl-RAC palmitoylation detection with palmitoylation inhibitors and mTORC1 assays; LAMTOR1/2 KO cells with bacterial infection assays; β-cell conditional KO with metabolic clamps

    PMID:30428163 PMID:31001086 PMID:31939616

    Open questions at the time
    • The palmitoyltransferase driving the dynamic signal was not identified at this stage
    • Direct biochemical role of LAMTOR1 in xenophagy receptor recruitment unclear
  11. 2020 High

    Intestinal conditional knockout with rapamycin phenocopy demonstrated that lysosomal mTORC1 anchored by LAMTOR1 is required for goblet cell differentiation, extending the scaffold to epithelial cell-fate decisions.

    Evidence Intestinal epithelium-specific conditional KO, mTORC1 localization assays, histology, organoids, rapamycin treatment

    PMID:32641600

    Open questions at the time
    • Transcriptional program downstream of mTORC1 driving goblet specification not defined
  12. 2021 Medium

    Vascular work showed LAMTOR1 induction is a node by which extracellular signals (platelet microvesicles via Src) drive mTORC1-dependent smooth muscle dedifferentiation and intimal hyperplasia.

    Evidence siRNA knockdown, SMC-specific conditional KO, mTORC1 phospho-readouts, Src inhibitor epistasis, in vivo injury model

    PMID:34604241

    Open questions at the time
    • Mechanism by which Src induces LAMTOR1 expression not detailed
  13. 2022 High

    A landmark expansion uncovered an mTORC1-independent function: LAMTOR1 directly inhibits TRPML1 via its N-terminus to control dendritic lysosome trafficking, synaptic plasticity and learning; concurrently, USP32-mediated deubiquitination and NMT1 myristoylation were shown to control LAMTOR1 v-ATPase engagement, stability and localization.

    Evidence Co-IP, in vivo CA1 deletion, Ca2+ imaging, decoy-peptide disruption, LTP and behavior; USP32 KO with ubiquitination/Co-IP/localization assays; NMT1 KO with Gly2 mutagenesis and stability assays

    PMID:34999170 PMID:35099830 PMID:36476874

    Open questions at the time
    • Structural basis of LAMTOR1–TRPML1 inhibition not resolved
    • How mTORC1-dependent and TRPML1-dependent functions are coordinated on the same scaffold unknown
  14. 2024 Medium

    The post-translational control circuit was completed and new degradative cargo functions emerged: TRAF4 K63-ubiquitinates LAMTOR1 at K151 to promote Rag binding, while LAMTOR1 was shown to route PD-L1 and cGAS to lysosomal degradation and to be transcriptionally controlled by Nrf2/p300 under oxidative stress upstream of TFEB.

    Evidence In vitro ubiquitination, K151R knock-in, TRAF4 KO with mTORC1 assays; Co-IP with HRS and cGAS, lysosomal degradation/exosome and interferon assays; promoter reporter, p300 inhibitor, TFEB localization with in vivo models

    PMID:38229144 PMID:39223601 PMID:39361643 PMID:39424220

    Open questions at the time
    • How K151 ubiquitination geometrically promotes Rag binding not structurally shown
    • Whether cargo-degradation roles depend on the Ragulator scaffold versus separable LAMTOR1 functions unclear
  15. 2025 Medium

    Chemical-biology approaches validated LAMTOR1 as a druggable node: the natural compound acacetin binds LAMTOR1 and releases it from the Ragulator to inhibit mTORC1 and induce autophagy, ameliorating hepatic lipid accumulation.

    Evidence DARTS/LC-MS target identification, CETSA, LAMTOR1 KD phenocopy, mTORC1/AMPK and autophagy assays, CDAHFD mouse model

    PMID:40548398

    Open questions at the time
    • Binding site of acacetin on LAMTOR1 not mapped
    • Whether compound directly disrupts a specific LAMTOR–LAMTOR interface unresolved
  16. 2026 Medium

    Identification of ZDHHC9 as the palmitoyltransferase acting on Cys3/Cys4 closed the loop on the dynamic palmitoylation observed earlier, linking a specific enzyme to mTORC1 recruitment in cancer.

    Evidence Palmitoylation assays, Cys3/4 mutagenesis, ZDHHC9 KO/KD, mTORC1 recruitment and Co-IP in renal cell carcinoma

    PMID:41856969

    Open questions at the time
    • How ZDHHC9 activity toward LAMTOR1 is itself regulated by amino acids not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the distinct mTORC1-scaffolding and TRPML1-inhibitory functions of a single small LAMTOR1 protein are spatially and temporally coordinated, and how the dense layer of lipid and ubiquitin modifications is switched in response to specific stimuli, remains unresolved.
  • No high-resolution structure of LAMTOR1 within the Ragulator or bound to TRPML1
  • The hierarchy and crosstalk among myristoylation, palmitoylation, K63/degradative ubiquitination, and deubiquitination is undefined
  • Whether the cytoplasmic Rho-activating and lysosomal scaffolding activities are physically separable is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2 GO:0005198 structural molecule activity 1
Localization
GO:0005764 lysosome 3 GO:0005768 endosome 3 GO:0005886 plasma membrane 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-168256 Immune System 4 R-HSA-9612973 Autophagy 4 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3
Partners
CGASHRSLAMTOR2LAMTOR3TRAF4TRPML1UBE3AUSP32
Complex memberships
Ragulator

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 LAMTOR1/p18 is a membrane protein specifically localized to the surface of late endosomes/lysosomes via N-terminal myristoylation and palmitoylation, where it serves as the anchor for the Ragulator complex (containing p14/LAMTOR2, MP1/LAMTOR3, HBXIP, and C7orf59). The Ragulator interacts with RagAB/CD GTPases and V-ATPase to activate mTORC1 on the lysosomal surface. The Ragulator also regulates a branch of the MAPK pathway by recruiting MEK1 to MP1/LAMTOR3. Biochemical fractionation, co-immunoprecipitation, membrane localization assays, review of prior experimental work Methods in enzymology High 24377928
2010 LAMTOR1 (Pdro/C11orf59) is localized to late endosomes/lysosomes through N-terminal myristoylation and palmitoylation. Depletion of LAMTOR1 by siRNA increases cellular free cholesterol content, accompanied by increased cholesterol efflux, stimulated LDL uptake, and increased cholesterol egress from late endosomes/lysosomes, indicating a role in cholesterol homeostasis. siRNA knockdown, stable overexpression, cholesterol measurement assays, subcellular fractionation, proteomic analysis of detergent-resistant membranes PloS one Medium 20544018
2010 LAMTOR1 (p27RF-Rho) promotes cancer metastasis by activating RhoA and RhoC, freeing RhoA from inhibition by cytoplasmic p27kip1. Knockdown of p27RF-Rho in metastatic melanoma cells markedly decreased lung metastasis, and p27RF-Rho regulated cellular adhesion, motility, and pericellular proteolysis through Rho activity. shRNA knockdown, in vivo mouse tail-vein metastasis assay, cell adhesion and motility assays, Rho activation assays The Journal of biological chemistry Medium 21087931
2012 LAMTOR1 depletion alters lysosomal activation: lysosomes become scattered in positioning but remain functional for cathepsin B maturation. LAMTOR1 loss stimulates autophagic flux, leading to excessive reactive oxygen species (ROS) production, which triggers p53-dependent cell cycle arrest and apoptosis. This lysosomal cell death pathway does not require mTORC1 activity. siRNA knockdown, immunofluorescence, ROS measurement, apoptosis assays, autophagic flux assays, p53 pathway analysis Cell death & disease Medium 22513874
2013 Conditional ablation of p18/LAMTOR1 in mouse epidermis attenuated lysosome function, resulting in accumulation of immature lysosomes and autophagosomes, and defective functional interaction between lysosomes and autophagosomes. This caused failure of corneocyte maturation and loss of skin barrier function, demonstrating that p18-mediated pathways control lysosome-mediated catabolic processes required for epidermal development. Conditional knockout mouse (Cre-lox), electron microscopy, cell culture lysosome behavior assays Journal of cell science High 23781028
2016 Lamtor1 forms an amino-acid sensing complex with lysosomal v-ATPase and serves as the scaffold for amino acid-activated mTORC1. Lamtor1 is critically required for M2 macrophage polarization; its deficiency, amino-acid starvation, or inhibition of v-ATPase and mTOR result in defective M2 and enhanced M1 polarization. Liver X receptor (LXR) and production of 25-hydroxycholesterol are identified as downstream targets of Lamtor1 and mTORC1 in this pathway. Conditional knockout mouse (myeloid-specific), macrophage polarization assays, pharmacological inhibition of v-ATPase and mTOR, 25-hydroxycholesterol measurements, LXR pathway analysis Nature communications High 27731330
2017 Lamtor1-deficient CD4+ T cells exhibit marked reductions in proliferation, IL-2 production, mTORC1 activity, and purine/lipid-synthesis gene expression. Th17 polarization, but not Th1/Th2, is diminished. Lamtor1-deficient regulatory T cells lose suppressive function and CTLA-4 expression, resulting in severe autoimmunity, indicating that Lamtor1 is essential for mTORC1-dependent T cell function. T cell-specific and Foxp3-specific conditional knockout mice, T cell polarization assays, proliferation assays, mTORC1 activity measurement, experimental autoimmune encephalomyelitis model Journal of immunology High 28768723
2018 UBE3A ubiquitinates p18/LAMTOR1, resulting in its proteasomal degradation. UBE3A deficiency (as in Angelman syndrome) leads to increased lysosomal localization of p18 and other Ragulator-Rag complex members and increased mTORC1 activity in hippocampal neurons. p18 knockdown in CA1 neurons of AS mice reduces elevated mTORC1 activity and improves dendritic spine maturation, LTP, and learning. Co-immunoprecipitation, ubiquitination assays, in vivo knockdown in AS mouse model, mTORC1 activity assays, electrophysiology (LTP), behavioral tests eLife High 30020076
2018 Lamtor1 controls innate immune responses by regulating mTORC1-dependent phosphorylation and nuclear translocation of TFEB (master regulator of lysosome/autophagosome biogenesis). Myeloid-specific Lamtor1 KO mice show nuclear TFEB translocation in alveolar macrophages and hypersensitivity to LPS and bleomycin. Myeloid-specific conditional knockout mouse, TFEB localization assays, LPS and bleomycin challenge models, immunofluorescence Journal of immunology High 29686050
2019 LAMTOR1 is directly palmitoylated (covalent lipid modification), and this palmitoylation is rapidly increased prior to mTORC1 activation by amino acids. Acute pharmacological inhibition of palmitoylation prevents amino acid-dependent mTORC1 activation in HEK293T cells and BDNF-dependent mTORC1 activation in hippocampal neurons, indicating that dynamic palmitoylation of LAMTOR1 is actively involved in mTORC1 signaling rather than merely permissive. Palmitoyl-proteomics, acyl-RAC assay (direct palmitoylation detection), pharmacological inhibition of palmitoylation, mTORC1 activity assays in HEK293T cells and primary hippocampal neurons Frontiers in cellular neuroscience Medium 31001086
2019 The LAMTOR2/LAMTOR1 complex regulates xenophagy against Group A Streptococcus and Salmonella. LAMTOR1 localizes to bacterium-containing endosomes; LAMTOR2 is recruited to damaged endosomes in a LAMTOR1-dependent manner. LAMTOR2 interacts with autophagy receptors NBR1, TAX1BP1, and p62, and is required for TAX1BP1 recruitment to pathogen-containing autophagosomes and autolysosome formation. Fluorescence microscopy, co-immunoprecipitation, LAMTOR1/2 knockout cells, bacterial infection assays, autolysosome formation assays Cellular microbiology Medium 30428163
2019 Loss of LAMTOR1 in pancreatic β-cells increases glucose-stimulated insulin secretion. LAMTOR1 KO leads to mitochondrial dysfunction but increases glutamate content in insulin granules and increases ACC1 (acetyl-CoA carboxylase 1) activity, thereby enhancing the amplification pathway of insulin secretion. β-cell-specific conditional knockout mouse, hyperglycemic clamp, islet perfusion, mitochondrial functional analysis, glutamate and ACC1 activity measurements International journal of molecular medicine Medium 31939616
2015 Depletion of p18/LAMTOR1 promotes cell survival under starvation by stimulating autophagy through modulation of p27kip1 activity. In p18-deficient MEF cells, phosphorylation of p27kip1 at Thr198 is elevated and LC3-II formation and other autophagy markers are increased. Suppression of p27kip1 in p18-deficient cells mitigates starvation-induced survival advantage. p18 knockout MEF cells, cell death assays, caspase-3 cleavage, LC3-II immunoblot, p27kip1 phosphorylation analysis, siRNA knockdown of p27kip1 Cell biology international Medium 26032166
2022 USP32 deubiquitinates LAMTOR1; USP32 knockout results in hyperubiquitination of LAMTOR1, which impairs its interaction with the vacuolar H+-ATPase, reduces Ragulator function, limits mTORC1 lysosomal recruitment, decreases mTORC1 activity, and induces autophagy. USP32 knockout (hTERT-RPE1 cells), ubiquitination assays, Co-immunoprecipitation (LAMTOR1–v-ATPase interaction), mTOR lysosomal localization by microscopy, mTORC1 activity assays, autophagy assays; C. elegans CYK-3 KD as ortholog validation Cell reports High 36476874
2022 LAMTOR1 directly interacts with TRPML1 through its N-terminal domain, tonically inhibiting TRPML1-mediated lysosomal Ca2+ release independently of mTORC1. LAMTOR1 deletion or disruption of LAMTOR1–TRPML1 binding increases Ca2+ release, facilitates dynein-powered lysosomal trafficking in dendrites, alters synaptic plasticity via calcineurin-mediated GluA1 dephosphorylation, and impairs learning and memory. Co-immunoprecipitation, LAMTOR1 deletion (hippocampal CA1 in vivo), Ca2+ imaging, TAT-decoy peptide disruption of interaction, lysosomal trafficking assays, LTP electrophysiology, behavioral tests (object recognition, fear conditioning) The EMBO journal High 35099830
2022 NMT1 myristoylates LAMTOR1 at Gly2, resulting in increased LAMTOR1 protein stability and lysosomal localization. NMT1 deficiency blocks LAMTOR1 myristoylation and inhibits mTORC1-dependent bladder cancer progression. NMT1 knockdown/knockout, myristoylation site mutagenesis (Gly2), subcellular fractionation, LAMTOR1 stability assays, in vitro and in vivo cancer progression assays, NMT1 inhibitor (B13) Cancer letters Medium 34999170
2024 TRAF4 directly interacts with LAMTOR1 and catalyzes K63-linked polyubiquitination of LAMTOR1 at K151 in an amino acid-dependent manner. This ubiquitination promotes LAMTOR1 binding to Rag GTPases and enhances mTORC1 activation. K151R knock-in or TRAF4 knockout blocks amino acid-induced mTORC1 activation. Co-immunoprecipitation, in vitro ubiquitination assay, K151R knock-in cells, TRAF4 knockout, mTORC1 activity assays, K63-linkage-specific ubiquitin analysis, in vivo colon cancer model Advanced science High 38229144
2024 LAMTOR1 interacts with HRS and facilitates PD-L1 lysosomal degradation, thereby reducing exosomal PD-L1 release. This function depends on a specific ubiquitination site and an HRS binding sequence on LAMTOR1. Co-immunoprecipitation (LAMTOR1–HRS interaction), PD-L1 lysosomal degradation assays, exosome quantification, LAMTOR1 domain/mutant analysis Molecular cancer Medium 39223601
2024 LAMTOR1 interacts with and promotes accumulation of cGAS in lysosomes upon chemotherapy-induced DNA fragment exposure, leading to cGAS degradation via the receptor protein p62. LAMTOR1 deficiency increases cGAS abundance and promotes cGAS-STING pathway activation and type I interferon production. Co-immunoprecipitation (LAMTOR1–cGAS interaction), LAMTOR1 knockout, cGAS abundance and stability assays, STING pathway activation measurement, interferon production assays, in vivo tumor models PNAS Medium 39361643
2020 p18/Lamtor1-mediated mTORC1 signaling on lysosomes is required for goblet cell differentiation in the intestinal epithelium. Conditional p18 KO in colonic crypts delocalizes mTORC1 from lysosomes, markedly decreases mTORC1 activity, increases proliferating cells, and dramatically reduces mucin-producing goblet cells. Rapamycin phenocopies goblet cell loss, confirming mTORC1 dependence. Intestinal epithelium-specific conditional knockout mouse, mTORC1 localization assays (lysosome fractionation/immunofluorescence), histology, colon crypt organoid culture, rapamycin treatment Cell structure and function High 32641600
2021 Platelet-derived microvesicles (PMVs) promote VSMC dedifferentiation via Src-dependent induction of Lamtor1, which activates mTORC1 signaling. Knockdown of Lamtor1 attenuates PMV-induced dedifferentiation, and SMC-specific Lamtor1 KO markedly attenuates intimal hyperplasia after vascular injury in vivo. siRNA knockdown, SMC-specific conditional knockout mouse, mTORC1 activity assays (S6K and 4E-BP1 phosphorylation), Src inhibitor experiments, in vivo intimal injury model Frontiers in cell and developmental biology Medium 34604241
2025 Binding of the natural compound acacetin (ACA) to LAMTOR1 induces LAMTOR1 release from the Ragulator complex, leading to mTORC1 inhibition and autophagy induction. Genetic knockdown of LAMTOR1 phenocopies ACA treatment, and this process modulates the mTORC1-AMPK axis to ameliorate lipid accumulation in MAFLD. DARTS (drug affinity responsive target stability) combined with LC-MS/MS proteomics identifying LAMTOR1 as ACA target, LAMTOR1 KD phenocopy, CETSA, mTORC1 and AMPK activity assays, autophagy flux assays, in vivo CDAHFD mouse model Autophagy Medium 40548398
2024 LAMTOR1 regulates lysosomal positioning in hippocampal neuronal dendrites through TRPML1 inhibition. LAMTOR1 knockdown increases lysosomal accumulation in proximal dendrites, reversible by TRPML1 KD, inhibition, or dynein inhibitor ciliobrevin D, indicating dynein-mediated transport downstream of TRPML1 activation. LAMTOR1 knockdown, TRPML1 knockdown, pharmacological TRPML1 activation (ML-SA1), TAT-decoy peptide disrupting LAMTOR1-TRPML1 binding, dynein inhibitor (ciliobrevin D), live imaging of lysosomal distribution in cultured hippocampal neurons Frontiers in cellular neuroscience Medium 39650798
2026 ZDHHC9 specifically palmitoylates LAMTOR1 at Cys3/Cys4 residues, enhancing mTORC1 recruitment to lysosomes and activating mTOR signaling in renal cell carcinoma. Palmitoylation assays, site-directed mutagenesis (Cys3/4), ZDHHC9 KO/KD, mTORC1 activity assays, co-immunoprecipitation Cell death & disease Medium 41856969
2024 Oxidative stress reduces LAMTOR1 protein predominantly through lysosomal degradation (reversible by lysosomal inhibitors pepstatin A and NH4Cl). Nrf2 positively regulates LAMTOR1 transcription through histone acetyltransferase p300-mediated histone acetylation. LAMTOR1 overexpression reverses 4-HNE-induced TFEB nuclear translocation, placing LAMTOR1 upstream of TFEB in this stress-response pathway. Pharmacological lysosomal inhibition (pepstatin A, NH4Cl), Nrf2 overexpression, luciferase reporter assay with lamtor1 promoter deletion mutants, p300 inhibitor, acetylated histone 3 immunoblot, TFEB localization assays, in vivo NaIO3 mouse model Experimental eye research Medium 39424220

Source papers

Stage 0 corpus · 35 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Polarization of M2 macrophages requires Lamtor1 that integrates cytokine and amino-acid signals. Nature communications 135 27731330
2018 UBE3A-mediated p18/LAMTOR1 ubiquitination and degradation regulate mTORC1 activity and synaptic plasticity. eLife 50 30020076
2013 The lysosomal signaling anchor p18/LAMTOR1 controls epidermal development by regulating lysosome-mediated catabolic processes. Journal of cell science 36 23781028
2019 mTORC1 Signaling Is Palmitoylation-Dependent in Hippocampal Neurons and Non-neuronal Cells and Involves Dynamic Palmitoylation of LAMTOR1 and mTOR. Frontiers in cellular neuroscience 35 31001086
2014 p18/LAMTOR1: a late endosome/lysosome-specific anchor protein for the mTORC1/MAPK signaling pathway. Methods in enzymology 35 24377928
2018 ADM Scaffolds Generate a Pro-regenerative Microenvironment During Full-Thickness Cutaneous Wound Healing Through M2 Macrophage Polarization via Lamtor1. Frontiers in physiology 28 29915541
2022 LAMTOR1 inhibition of TRPML1-dependent lysosomal calcium release regulates dendritic lysosome trafficking and hippocampal neuronal function. The EMBO journal 25 35099830
2022 N-myristoyltransferase-1 deficiency blocks myristoylation of LAMTOR1 and inhibits bladder cancer progression. Cancer letters 22 34999170
2022 USP32-regulated LAMTOR1 ubiquitination impacts mTORC1 activation and autophagy induction. Cell reports 22 36476874
2012 LAMTOR1 depletion induces p53-dependent apoptosis via aberrant lysosomal activation. Cell death & disease 22 22513874
2010 A p27(kip1)-binding protein, p27RF-Rho, promotes cancer metastasis via activation of RhoA and RhoC. The Journal of biological chemistry 22 21087931
2019 LAMTOR2/LAMTOR1 complex is required for TAX1BP1-mediated xenophagy. Cellular microbiology 21 30428163
2018 Lysosomal Protein Lamtor1 Controls Innate Immune Responses via Nuclear Translocation of Transcription Factor EB. Journal of immunology (Baltimore, Md. : 1950) 21 29686050
2024 TRAF4-Mediated LAMTOR1 Ubiquitination Promotes mTORC1 Activation and Inhibits the Inflammation-Induced Colorectal Cancer Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20 38229144
2024 LAMTOR1 decreased exosomal PD-L1 to enhance immunotherapy efficacy in non-small cell lung cancer. Molecular cancer 20 39223601
2019 Loss of LAMTOR1 in pancreatic β‑cells increases glucose‑stimulated insulin secretion in mice. International journal of molecular medicine 20 31939616
2010 Pdro, a protein associated with late endosomes and lysosomes and implicated in cellular cholesterol homeostasis. PloS one 20 20544018
2015 LAMTOR1-PRKCD and NUMA1-SFMBT1 fusion genes identified by RNA sequencing in aneurysmal benign fibrous histiocytoma with t(3;11)(p21;q13). Cancer genetics 18 26432191
2017 Lamtor1 Is Critically Required for CD4+ T Cell Proliferation and Regulatory T Cell Suppressive Function. Journal of immunology (Baltimore, Md. : 1950) 16 28768723
2022 LAMTOR1 degrades MHC-II via the endocytic in hepatocellular carcinoma. Carcinogenesis 11 36070764
2021 Platelet-Derived Microvesicles Promote VSMC Dedifferentiation After Intimal Injury via Src/Lamtor1/mTORC1 Signaling. Frontiers in cell and developmental biology 11 34604241
2015 Depletion of p18/LAMTOR1 promotes cell survival via activation of p27(kip1) -dependent autophagy under starvation. Cell biology international 11 26032166
2021 Macrophage LAMTOR1 Deficiency Prevents Dietary Obesity and Insulin Resistance Through Inflammation-Induced Energy Expenditure. Frontiers in cell and developmental biology 9 34095141
2025 Inhibition of lysosomal LAMTOR1 increases autophagy by suppressing the MTORC1 pathway to ameliorate lipid accumulations in MAFLD. Autophagy 7 40548398
2024 LAMTOR1 ablation impedes cGAS degradation caused by chemotherapy and promotes antitumor immunity. Proceedings of the National Academy of Sciences of the United States of America 7 39361643
2022 Arterial cyclic stretch regulates Lamtor1 and promotes neointimal hyperplasia via circSlc8a1/miR-20a-5p axis in vein grafts. Theranostics 7 35836818
2010 Comparative analysis of fat and muscle proteins in fenofibrate-fed type II diabetic OLETF rats: the fenofibrate-dependent expression of PEBP or C11orf59 protein. BMB reports 6 20510017
2018 Roles of Lamtor1 in Macrophages, CD4+ T-cells, and Regulatory T-cells. Critical reviews in immunology 5 30806216
2020 p18/Lamtor1-mTORC1 Signaling Controls Development of Mucin-producing Goblet Cells in the Intestine. Cell structure and function 4 32641600
2024 Regulation of LAMTOR1 by oxidative stress in retinal pigment epithelium: Implications for age-related macular degeneration pathogenesis. Experimental eye research 3 39424220
2024 LAMTOR1/mTORC1 promotes CD276 to induce immunosuppression via PI3K/Akt/MMP signaling pathway in Clostridium perfringens-induced necrotic enteritis of laying hens. Poultry science 2 39270482
2017 Lentivirus-mediated knockdown of P27RF-Rho inhibits hepatocellular carcinoma cell growth. Contemporary oncology (Poznan, Poland) 2 28435396
2024 LAMTOR1 regulates dendritic lysosomal positioning in hippocampal neurons through TRPML1 inhibition. Frontiers in cellular neuroscience 1 39650798
2021 [Identification of LAMTOR1-regulated metabolites using ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry in malignant transformation of liver inflammation]. Se pu = Chinese journal of chromatography 1 34505434
2026 ZDHHC9 palmitoylates LAMTOR1 to promote renal cell carcinoma malignant progression. Cell death & disease 0 41856969

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