ArticleFrontiers in cellular neuroscience2019
mTORC1 Signaling Is Palmitoylation-Dependent in Hippocampal Neurons and Non-neuronal Cells and Involves Dynamic Palmitoylation of LAMTOR1 and mTOR.
Article in Frontiers in cellular neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- zDHHC21 loss of function activates lung fibroblasts by regulating PTEN palmitoylation.American journal of respiratory cell and molecular biology · 2026Article
- ZDHHC9 palmitoylates LAMTOR1 to promote renal cell carcinoma malignant progression.Cell death & disease · 2026Article
- Mechanisms of mTORC1 and GCN2 amino acid sensing pathways in tumorigenesis and metastatic progression (Review).International journal of molecular medicine · 2026Review
- Palmitic acid and palmitoylation in cancer: Understanding, insights, and challenges.Innovation (Cambridge (Mass.)) · 2025Review
- Reduced Palmitoylation of SQSTM1/p62 in Huntington Disease Is Associated With Impaired Autophagy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- High-fat stimulation induces atrial structural remodeling via the TPM1/P53/SHISA5 Axis.Lipids in health and disease · 2025Article
- Regulation of autophagy by protein lipidation.Advanced biotechnology · 2024Review
- Recruitment, regulation, and release: Control of signaling enzyme localization and function by reversible S-acylation.The Journal of biological chemistry · 2024Review
- Mechanisms and functions of protein S-acylation.Nature reviews. Molecular cell biology · 2024Review
- TRAF4-Mediated LAMTOR1 Ubiquitination Promotes mTORC1 Activation and Inhibits the Inflammation-Induced Colorectal Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Refining S-acylation: Structure, regulation, dynamics, and therapeutic implications.The Journal of cell biology · 2023Article
- Review
- The Ragulator complex: delving its multifunctional impact on metabolism and beyond.Inflammation and regeneration · 2023Review
- Lost in traffic: consequences of altered palmitoylation in neurodegeneration.Frontiers in physiology · 2023Review
- Structural Exploration on Palmitoyltransferase DHHC3 fromPolymers · 2022Article
- SHISA5/SCOTIN restrains spontaneous autophagy induction by blocking contact between the ERES and phagophores.Autophagy · 2022Article
- Article
- The needs of a synapse-How local organelles serve synaptic proteostasis.The EMBO journal · 2022Review
- Reconstruction and Exploratory Analysis of mTORC1 Signaling Pathway and Its Applications to Various Diseases Using Network-Based Approach.Journal of microbiology and biotechnology · 2022Article
- Inhibitors of DHHC family proteins.Current opinion in chemical biology · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanistic target of rapamycin (mTOR) Complex 1 (mTORC1) controls growth and proliferation of non-neuronal cells, while during neuronal development mTORC1 responds to glutamate and neurotrophins to promote neuronal migration and dendritic arborization. Recent studies reveal that mTORC1 signaling complexes are assembled on lysosomal membranes, but how mTORC1 membrane targeting is regulated is not fully clear. Our examination of palmitoyl-proteomic databases and additional bioinformatic analyses revealed that several mTORC1 proteins are predicted to undergo covalent modification with the lipid palmitate. This process, palmitoylation, can dynamically target proteins to specific membranes but its roles in mTORC1 signaling are not well described. Strikingly, we found that acute pharmacological inhibition of palmitoylation prevents amino acid-dependent mTORC1 activation in HEK293T cells and brain-derived neurotrophic factor (BDNF)-dependent mTORC1 activation in hippocampal neurons. We sought to define the molecular basis for this finding and found that the mTORC1 proteins LAMTOR1 and mTOR itself are directly palmitoylated, while several other mTORC1 proteins are not palmitoylated, despite strong bioinformatic prediction. Interestingly, palmitoylation of LAMTOR1, whose anchoring on lysosomal membranes is important for mTORC1 signaling, was rapidly increased prior to mTORC1 activation. In contrast, mTOR palmitoylation was decreased by stimuli that activate mTORC1. These findings reveal that specific key components of the mTOR pathway are dynamically palmitoylated, suggesting that palmitoylation is not merely permissive for mTOR activation but is instead actively involved in mTORC1-dependent signaling.
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Registered trials
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