The Drosophila Nesprin-1 homolog MSP300 is required for muscle autophagy and proteostasis

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dc.citation.articleNumberjcs262096en_US
dc.citation.issueNumber11en_US
dc.citation.journalTitleJournal of Cell Scienceen_US
dc.citation.volumeNumber137en_US
dc.contributor.authorvan der Graaf, Kevinen_US
dc.contributor.authorSrivastav, Saurabhen_US
dc.contributor.authorNishad, Rajkishoren_US
dc.contributor.authorStern, Michaelen_US
dc.contributor.authorMcNew, James A.en_US
dc.date.accessioned2024-11-04T16:25:12Zen_US
dc.date.available2024-11-04T16:25:12Zen_US
dc.date.issued2024en_US
dc.description.abstractNesprin proteins, which are components of the linker of nucleoskeleton and cytoskeleton (LINC) complex, are located within the nuclear envelope and play prominent roles in nuclear architecture. For example, LINC complex proteins interact with both chromatin and the cytoskeleton. Here, we report that the Drosophila Nesprin MSP300 has an additional function in autophagy within larval body wall muscles. RNAi-mediated MSP300 knockdown in larval body wall muscles resulted in defects in the contractile apparatus, muscle degeneration and defective autophagy. In particular, MSP300 knockdown caused accumulation of cytoplasmic aggregates that contained poly-ubiquitylated cargo, as well as the autophagy receptor ref(2)P (the fly homolog of p62 or SQSTM) and Atg8a. Furthermore, MSP300 knockdown larvae expressing an mCherry–GFP-tagged Atg8a transgene exhibited aberrant persistence of the GFP signal within these aggregates, indicating failure of autophagosome maturation. These autophagy deficits were similar to those exhibited by loss of the endoplasmic reticulum (ER) fusion protein Atlastin (Atl), raising the possibility that Atl and MSP300 might function in the same pathway. In support of this possibility, we found that a GFP-tagged MSP300 protein trap exhibited extensive localization to the ER. Alteration of ER-directed MSP300 might abrogate important cytoskeletal contacts necessary for autophagosome completion.en_US
dc.identifier.citationvan der Graaf, K., Srivastav, S., Nishad, R., Stern, M., & McNew, J. A. (2024). The Drosophila Nesprin-1 homolog MSP300 is required for muscle autophagy and proteostasis. Journal of Cell Science, 137(11), jcs262096. https://doi.org/10.1242/jcs.262096en_US
dc.identifier.digitaljcs262096en_US
dc.identifier.doihttps://doi.org/10.1242/jcs.262096en_US
dc.identifier.urihttps://hdl.handle.net/1911/117996en_US
dc.language.isoengen_US
dc.publisherThe Company of Biologistsen_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license. Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleThe Drosophila Nesprin-1 homolog MSP300 is required for muscle autophagy and proteostasisen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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