Many cancer cells exhibit increased amounts of paucimannose glycans, which are truncated N-glycan structures rarely found in mammals. Paucimannosidic proteins are proposedly generated within lysosomes and exposed on the cell surface through a yet uncertain mechanism. In this study, we revealed that paucimannosidic proteins are produced by lysosomal glycosidases and secreted via lysosomal exocytosis. Interestingly, lysosomal exocytosis preferentially occurred in the vicinity of focal adhesions, protein complexes connecting the actin cytoskeleton to the extracellular matrix. Through genome-wide knockout screening, we identified that MYO18B, an actin crosslinker, is required for focal adhesion maturation, facilitating lysosomal exocytosis and the release of paucimannosidic lysosomal proteins to the extracellular milieu. Moreover, a mechanosensitive cation channel PIEZO1 locally activated at focal adhesions imports Ca2+ necessary for lysosome-plasma membrane fusion. Collectively, our study unveiled an intimate relationship between lysosomal exocytosis and focal adhesion, shedding light on the unexpected interplay between lysosomal activities and cellular mechanosensing.
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January 03 2025
MYO18B promotes lysosomal exocytosis by facilitating focal adhesion maturation
Wei-Wei Ren
,
Wei-Wei Ren
(Conceptualization, Investigation, Methodology, Writing - original draft)
1Key Laboratory of Carbohydrate Chemistry and Biotechnology,
Ministry of Education, School of Biotechnology, Jiangnan University
, Wuxi, China
2
Institute for Glyco-core Research (iGCORE), Gifu University
, Gifu, Japan
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Rebeca Kawahara
,
Rebeca Kawahara
(Formal analysis, Methodology)
3
Institute for Glyco-core Research (iGCORE), Nagoya University
, Aichi, Japan
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Kenichi G.N. Suzuki
,
Kenichi G.N. Suzuki
(Methodology, Writing - review & editing)
2
Institute for Glyco-core Research (iGCORE), Gifu University
, Gifu, Japan
4Division of Advanced Bioimaging,
National Cancer Center Research Institute
, Tokyo, Japan
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Priya Dipta
,
Priya Dipta
(Conceptualization, Formal analysis, Investigation)
5School of Natural Sciences,
Macquarie University
, Sydney, Australia
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Ganglong Yang
,
Ganglong Yang
(Data curation, Methodology, Supervision, Writing - review & editing)
1Key Laboratory of Carbohydrate Chemistry and Biotechnology,
Ministry of Education, School of Biotechnology, Jiangnan University
, Wuxi, China
6State Key Laboratory of Biochemical Engineering,
Institute of Process Engineering, Chinese Academy of Sciences
, Beijing, China
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Morten Thaysen-Andersen
,
Morten Thaysen-Andersen
(Investigation, Supervision, Validation, Writing - original draft, Writing - review & editing)
3
Institute for Glyco-core Research (iGCORE), Nagoya University
, Aichi, Japan
5School of Natural Sciences,
Macquarie University
, Sydney, Australia
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Morihisa Fujita
(Conceptualization, Funding acquisition, Project administration, Supervision, Writing - original draft, Writing - review & editing)
1Key Laboratory of Carbohydrate Chemistry and Biotechnology,
Ministry of Education, School of Biotechnology, Jiangnan University
, Wuxi, China
2
Institute for Glyco-core Research (iGCORE), Gifu University
, Gifu, Japan
Correspondence to Morihisa Fujita: [email protected]
Search for other works by this author on:
Wei-Wei Ren
Conceptualization, Investigation, Methodology, Writing - original draft
1Key Laboratory of Carbohydrate Chemistry and Biotechnology,
Ministry of Education, School of Biotechnology, Jiangnan University
, Wuxi, China
2
Institute for Glyco-core Research (iGCORE), Gifu University
, Gifu, Japan
Rebeca Kawahara
Formal analysis, Methodology
3
Institute for Glyco-core Research (iGCORE), Nagoya University
, Aichi, Japan
Kenichi G.N. Suzuki
Methodology, Writing - review & editing
2
Institute for Glyco-core Research (iGCORE), Gifu University
, Gifu, Japan
4Division of Advanced Bioimaging,
National Cancer Center Research Institute
, Tokyo, Japan
Priya Dipta
Conceptualization, Formal analysis, Investigation
5School of Natural Sciences,
Macquarie University
, Sydney, Australia
Ganglong Yang
Data curation, Methodology, Supervision, Writing - review & editing
1Key Laboratory of Carbohydrate Chemistry and Biotechnology,
Ministry of Education, School of Biotechnology, Jiangnan University
, Wuxi, China
6State Key Laboratory of Biochemical Engineering,
Institute of Process Engineering, Chinese Academy of Sciences
, Beijing, China
Morten Thaysen-Andersen
Investigation, Supervision, Validation, Writing - original draft, Writing - review & editing
3
Institute for Glyco-core Research (iGCORE), Nagoya University
, Aichi, Japan
5School of Natural Sciences,
Macquarie University
, Sydney, Australia
Morihisa Fujita
Conceptualization, Funding acquisition, Project administration, Supervision, Writing - original draft, Writing - review & editing
1Key Laboratory of Carbohydrate Chemistry and Biotechnology,
Ministry of Education, School of Biotechnology, Jiangnan University
, Wuxi, China
2
Institute for Glyco-core Research (iGCORE), Gifu University
, Gifu, Japan
Correspondence to Morihisa Fujita: [email protected]
Disclosures: The authors declare no competing interests exist.
Received:
July 11 2024
Revision Received:
October 17 2024
Accepted:
December 02 2024
Online ISSN: 1540-8140
Print ISSN: 0021-9525
Funder(s):
Japan Society for the Promotion of Science
- Award Id(s): 21K21346,JPJSCCA202000007
Funder(s):
National Natural Science Foundation of China
- Award Id(s): 32071278
Funder(s):
Ministry of Education, Culture, Sports, Science and Technology
Funder(s):
Takeda Science Foundation
© 2025 Crown copyright. The government of Australia, Canada, or the UK ("the Crown") owns the copyright interests of authors who are government employees. The Crown Copyright is not transferable.
2025
Crown copyright. The government of Australia, Canada, or the UK ("the Crown") owns the copyright interests of authors who are government employees. The Crown Copyright is not transferable.
This article is distributed under the terms as described at https://rupress.org/pages/terms102024/.
J Cell Biol (2025) 224 (3): e202407068.
Article history
Received:
July 11 2024
Revision Received:
October 17 2024
Accepted:
December 02 2024
Citation
Wei-Wei Ren, Rebeca Kawahara, Kenichi G.N. Suzuki, Priya Dipta, Ganglong Yang, Morten Thaysen-Andersen, Morihisa Fujita; MYO18B promotes lysosomal exocytosis by facilitating focal adhesion maturation. J Cell Biol 3 March 2025; 224 (3): e202407068. doi: https://doi.org/10.1083/jcb.202407068
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