Detyrosinated microtubules spatially constrain lysosomes facilitating lysosome-autophagosome fusion
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Microtubule post-translational modifications impart functional diversity to microtubules by affecting their dynamics, organization, and interaction with proteins. Using super-resolution microscopy, we show that only a small subpopulation of microtubules are detyrosinated in epithelial cells, while acetylated and tyrosinated microtubules comprise the majority of all microtubules. Surprisingly, lysosomes are enriched by approximately threefold on detyrosinated microtubules. Further, their motility on detyrosinated microtubules is impaired, showing shorter runs and more frequent and longer pauses. Lysosome enrichment is mediated through a kinesin-1-dependent mechanism, since knocking down this motor abolishes enrichment. Finally, correlative live-cell and super-resolution microscopy showed that lysosomes interact with autophagosomes on detyrosinated microtubules. Removal of detyrosinated microtubules or knockdown of kinesin-1 leads to a decrease in the percentage of autolysosomes, a fusion intermediate of autophagosomes and lysosomes. Taken together, our data reveal a new role of detyrosinated microtubules as hubs that spatially concentrate lysosomes on a small subset of microtubules and facilitate their interaction and fusion with autophagosomes to initiate autophagy.
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Dynamic microtubules (marked by tyrosination) are required for efficient transport of autophagosomes, whereas stable microtubules (marked by acetylation) hinder autophagosome trafficking.
“Dynamic microtubules (marked by tyrosination) are required for efficient transport of autophagosomes, whereas stable microtubules (marked by acetylation) hinder autophagosome trafficking (Toops et al., 2015; Mohan et al., 2019).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Mohan et al., 2019
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- Authors
- Mohan, N., Sorokina, E. M., Verdeny, I. V., Alvarez, A. S., & Lakadamyali, M.
- Affiliations
- University of Pennsylvania (US)
- Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, Spain 2
- Institute of Photonic Sciences (ES)
- Corresponding author
- Lakadamyali, Melike
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2018-12-19
- Volume
- 218
- Issue
- 2
- Pages
- 632-643
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC6363446
- OpenAlex
- W2905019809
- Cited by
- 92
- References
- 44
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 11 · 2023: 13 · 2022: 12 · 2021: 15 · 2020: 11 · 2019: 7
- FWCI
- 4.57
- 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
- Perelman School of Medicine, University of Pennsylvania
- European Research Council (337191-MOTORS)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- lysosome motility, autophagy, kinesin-1, microtubule acetylation, autolysosomes, epithelial cells
- MeSH terms
- Autophagosomes, Acetylation, Animals, Cell Line, Chlorocebus aethiops, Epithelial Cells, Kidney, Lysosomes, Membrane Fusion, Microtubules, Protein Processing, Post-Translational, Tubulin, Tyrosine, Kinesins
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