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Failure of lysosome clustering and positioning in the juxtanuclear region in cells deficient in rapsyn
Abstract
Rapsyn, a scaffold protein, is required for the clustering of acetylcholine receptors (AChRs) at contacts between motor neurons and differentiating muscle cells. Rapsyn is also expressed in cells that do not express AChRs. However, its function in these cells remains unknown. Here, we showed that rapsyn plays an AChR-independent role in organizing the distribution and mobility of lysosomes. In cells devoid of AChRs, rapsyn selectively induced the clustering of lysosomes at high density in the juxtanuclear region without affecting the distribution of other intracellular organelles. However, when the same cells overexpress AChRs, rapsyn is recruited away from lysosomes to co-localize with AChR clusters on the cell surface. In rapsyn-deficient (rapsyn−/−) myoblasts or cells overexpressing rapsyn mutants, lysosomes are scattered within the cell and highly dynamic. The increased mobility of lysosomes in rapsyn−/− cells is associated with a significant increase of lysosomal exocytosis as evidenced by increased release of lysosomal enzymes and the plasma membrane damage when cells were challenged with the bacterial pore-forming toxin streptolysin-O. These findings uncover a new link between rapsyn, lysosome positioning, exocytosis, and plasma membrane integrity.
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Overexpression of Rab34, Rab36, Rabring7, or Rapsyn causes clustering of lysosomes in the perinuclear area.
“overexpression of Rab34, Rab36, Rabring7, or Rapsyn causes clustering of lysosomes in the perinuclear area.”
From TFEB regulates lysosomal positioning by modulating TMEM55B expression and JIP4 recruitment to lysosomes (2017) · cites this paper as [33]
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Willett, R., Martina, J. A., Zewe, J. P., Wills, R., Hammond, G. R. V., & Puertollano, R. (2017) · Nature Communications · doi:10.1038/s41467-017-01871-z · Cited by 201
TMEM55B downregulation promotes neurodegeneration in Alzheimer’s disease models
Roy, B., Contu, V. R., Jeziorek, M., Friedman, W. J., & Wong, C.-O. (2026) · doi:10.64898/2026.10.21.760809
Metadata
- Authors
- Aittaleb, M., Chen, P.-J., & Akaaboune, M.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2015-01-01
- ISSN
- 1477-9137
- 0021-9533
- Cited by
- 14
- References
- 2
- Language
- en
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