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dc.contributor.authorBawa, Simranjot
dc.contributor.authorGameros, Samantha
dc.contributor.authorBaumann, Kenny
dc.contributor.authorBrooks, David S.
dc.contributor.authorKollhoff, Joseph A.
dc.contributor.authorZolkiewski, Michal
dc.contributor.authorCecconi, Andrea David Re
dc.contributor.authorPanini, Nicolò
dc.contributor.authorRusso, Massimo
dc.contributor.authorPiccirillo, Rosanna
dc.contributor.authorJohnson, David K.
dc.contributor.authorKashipathy, Maithri M.
dc.contributor.authorBattaile, Kevin P.
dc.contributor.authorLovell, Scott
dc.contributor.authorBouyain, Samuel E. A.
dc.contributor.authorKawakami, Jessica
dc.contributor.authorGeisbrecht, Erika R.
dc.date.accessioned2022-01-05T21:18:42Z
dc.date.available2022-01-05T21:18:42Z
dc.date.issued2021-01-28
dc.identifier.citationBawa, S., Gameros, S., Baumann, K., Brooks, D. S., Kollhoff, J. A., Zolkiewski, M., Re Cecconi, A. D., Panini, N., Russo, M., Piccirillo, R., Johnson, D. K., Kashipathy, M. M., Battaile, K. P., Lovell, S., Bouyain, S., Kawakami, J., & Geisbrecht, E. R. (2021). Costameric integrin and sarcoglycan protein levels are altered in a Drosophila model for Limb-girdle muscular dystrophy type 2H. Molecular biology of the cell, 32(3), 260–273. https://doi.org/10.1091/mbc.E20-07-0453en_US
dc.identifier.urihttp://hdl.handle.net/1808/32344
dc.description.abstractMutations in two different domains of the ubiquitously expressed TRIM32 protein give rise to two clinically separate diseases, one of which is Limb-girdle muscular dystrophy type 2H (LGMD2H). Uncovering the muscle-specific role of TRIM32 in LGMD2H pathogenesis has proven difficult, as neurogenic phenotypes, independent of LGMD2H pathology, are present in TRIM32 KO mice. We previously established a platform to study LGMD2H pathogenesis using Drosophila melanogaster as a model. Here we show that LGMD2H disease-causing mutations in the NHL domain are molecularly and structurally conserved between fly and human TRIM32. Furthermore, transgenic expression of a subset of myopathic alleles (R394H, D487N, and 520fs) induce myofibril abnormalities, altered nuclear morphology, and reduced TRIM32 protein levels, mimicking phenotypes in patients afflicted with LGMD2H. Intriguingly, we also report for the first time that the protein levels of βPS integrin and sarcoglycan δ, both core components of costameres, are elevated in TRIM32 disease-causing alleles. Similarly, murine myoblasts overexpressing a catalytically inactive TRIM32 mutant aberrantly accumulate α- and β-dystroglycan and α-sarcoglycan. We speculate that the stoichiometric loss of costamere components disrupts costamere complexes to promote muscle degeneration.en_US
dc.publisherSpringer Natureen_US
dc.rights© 2021 Bawa et al. This article is distributed by The American Society for Cell Biology under license from the author(s). This work is licensed under a Creative Commons Attribution-NonCommercial ShareAlike 3.0 International License.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/3.0/en_US
dc.titleCostameric integrin and sarcoglycan protein levels are altered in a Drosophila model for Limb-girdle muscular dystrophy type 2Hen_US
dc.typeArticleen_US
kusw.kuauthorJohnson, David K.
kusw.kuauthorKashipathy, Maithri M.
kusw.kuauthorLovell, Scott
kusw.kudepartmentMolecular Graphics and Modeling Laboratoryen_US
kusw.kudepartmentComputational Chemical Biology Coreen_US
kusw.kudepartmentProtein Structure Laboratoryen_US
dc.identifier.doi10.1091/mbc.E20-07-0453en_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC8098830en_US
dc.rights.accessrightsopenAccessen_US


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© 2021 Bawa et al. This article is distributed by The American Society for Cell Biology under license from the author(s). This work is licensed under a Creative Commons Attribution-NonCommercial ShareAlike 3.0 International License.
Except where otherwise noted, this item's license is described as: © 2021 Bawa et al. This article is distributed by The American Society for Cell Biology under license from the author(s). This work is licensed under a Creative Commons Attribution-NonCommercial ShareAlike 3.0 International License.