LAMTOR/Ragulator is a negative regulator of Arl8b- and BORC-dependent late endosomal positioning
Open accessAbstract
Signaling from lysosomes controls cellular clearance and energy metabolism. Lysosomal malfunction has been implicated in several pathologies, including neurodegeneration, cancer, infection, immunodeficiency, and obesity. Interestingly, many functions are dependent on the organelle position. Lysosomal motility requires the integration of extracellular and intracellular signals that converge on a competition between motor proteins that ultimately control lysosomal movement on microtubules. Here, we identify a novel upstream control mechanism of Arl8b-dependent lysosomal movement toward the periphery of the cell. We show that the C-terminal domain of lyspersin, a subunit of BLOC-1–related complex (BORC), is essential and sufficient for BORC-dependent recruitment of Arl8b to lysosomes. In addition, we establish lyspersin as the linker between BORC and late endosomal/lysosomal adaptor and mitogen activated protein kinase and mechanistic target of rapamycin activator (LAMTOR) complexes and show that epidermal growth factor stimulation decreases LAMTOR/BORC association, thereby promoting BORC- and Arl8b-dependent lysosomal centrifugal transport.
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BORC has been implicated in regulating lysosome positioning in concert with amino acid signaling through Ragulator-Rag and also lysosome-autophagosome fusion during autophagy.
“BORC has been implicated in regulating lysosome positioning in concert with amino acid signaling through Ragulator-Rag (Filipek et al., 2017; Pu et al., 2017) and also lysosome-autophagosome fusion during autophagy (Jia et al., 2017)”
From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as Filipek et al., 2017
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- Authors
- Filipek, P. A., de Araujo, M. E. G., Vogel, G. F., De Smet, C. H., Eberharter, D., Rebsamen, M., Rudashevskaya, E. L., Kremser, L., Yordanov, T., Tschaikner, P., Fürnrohr, B. G., Lechner, S., Dunzendorfer-Matt, T., Scheffzek, K., Bennett, K. L., Superti-Furga, G., Lindner, H. H., Stasyk, T., & Huber, L. A.
- Affiliations
- Innsbruck Medical University (AT)
- Division of Cell Biology, Biocenter, Innsbruck Medical University, Innsbruck, Austria 1
- Austrian Academy of Sciences (AT)
- Universität Innsbruck (AT)
- CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria 5
- Corresponding author
- Stasyk, Taras
- Huber, Lukas A.
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2017-10-09
- Volume
- 216
- Issue
- 12
- Pages
- 4199-4215
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC5716276
- OpenAlex
- W2763953806
- Cited by
- 119
- References
- 78
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- 2026: 6 · 2025: 8 · 2024: 7 · 2023: 18 · 2022: 14 · 2021: 16 · 2020: 18 · 2019: 20 · 2018: 11 · 2017: 1
- FWCI
- 7.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Austrian Science Fund
- Innsbruck Medical University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- Arl8b, EGF signaling, microtubule motor proteins, lysosomal signaling
- MeSH terms
- Carrier Proteins, Epidermal Growth Factor, Gene Expression Regulation, HeLa Cells, Humans, Lysosomes, Microtubules, Movement, Nerve Tissue Proteins, Endosomes, Signal Transduction, Protein Isoforms, ADP-Ribosylation Factors, Protein Transport, Multiprotein Complexes, Intracellular Signaling Peptides and Proteins, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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