ArticleThe Journal of cell biology2017
A Ragulator-BORC interaction controls lysosome positioning in response to amino acid availability.
Article in The Journal of cell biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 127 citations in OpenAlex.
- Kinesins in Cancer Drug Resistance: Mechanisms, Therapeutic Targeting, and Translational Potential.Cancers · 2026Review
- LRRK2: Molecular Mechanisms in Parkinson's Disease.International journal of molecular sciences · 2026Review
- BORC assemblies integrate BLOC-1 subunits to diversify endosomal trafficking functions.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Peripheral lysosome levels dictate mTORC1 inactivation even when catabolically impaired.Cell communication and signaling : CCS · 2026Article
- BLOC1S1 Attenuates B. Melitensis 16M LPS-Triggered Autophagy by Spatial Confinement of TDP-43.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Programmed ribosomal frameshifting duringScience advances · 2025Article
- BLOC-1 and BORC: Complex regulators of endolysosomal dynamics.Cell chemical biology · 2025Review
- Heterogeneity of late endosome/lysosomes shown by multiplexed DNA-PAINT imaging.The Journal of cell biology · 2025Article
- 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 · 2024Article
- Chemical genetic screens reveal defective lysosomal trafficking as synthetic lethal with NF1 loss.Journal of cell science · 2024Article
- Biallelic BORCS8 variants cause an infantile-onset neurodegenerative disorder with altered lysosome dynamics.Brain : a journal of neurology · 2024Article
- Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology.Nature reviews. Molecular cell biology · 2024Review
- DENND6A links Arl8b to a Rab34/RILP/dynein complex, regulating lysosomal positioning and autophagy.Nature communications · 2024Article
- LAMTOR1 regulates dendritic lysosomal positioning in hippocampal neurons through TRPML1 inhibition.Frontiers in cellular neuroscience · 2024Article
- Organelle Communication with the Nucleus.Results and problems in cell differentiation · 2024Review
- RUFY3 regulates endolysosomes perinuclear positioning, antigen presentation and migration in activated phagocytes.Nature communications · 2023Article
- Inhibition of endolysosome fusion increases exosome secretion.The Journal of cell biology · 2023Article
- Multi-omic approach characterises the neuroprotective role of retromer in regulating lysosomal health.Nature communications · 2023Article
- The Ragulator complex: delving its multifunctional impact on metabolism and beyond.Inflammation and regeneration · 2023Review
- The lysosomal LAMTOR / Ragulator complex is essential for nutrient homeostasis in brown adipose tissue.Molecular metabolism · 2023Article
12 more citing papers are in PubMed but not listed here.
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3 authors at 1 institution in 1 country.
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Abstract
Lysosomes play key roles in the cellular response to amino acid availability. Depletion of amino acids from the medium turns off a signaling pathway involving the Ragulator complex and the Rag guanosine triphosphatases (GTPases), causing release of the inactive mammalian target of rapamycin complex 1 (mTORC1) serine/threonine kinase from the lysosomal membrane. Decreased phosphorylation of mTORC1 substrates inhibits protein synthesis while activating autophagy. Amino acid depletion also causes clustering of lysosomes in the juxtanuclear area of the cell, but the mechanisms responsible for this phenomenon are poorly understood. Herein we show that Ragulator directly interacts with BLOC-1-related complex (BORC), a multi-subunit complex previously found to promote lysosome dispersal through coupling to the small GTPase Arl8 and the kinesins KIF1B and KIF5B. Interaction with Ragulator exerts a negative regulatory effect on BORC that is independent of mTORC1 activity. Amino acid depletion strengthens this interaction, explaining the redistribution of lysosomes to the juxtanuclear area. These findings thus demonstrate that amino acid availability controls lysosome positioning through Ragulator-dependent, but mTORC1-independent, modulation of BORC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.