The Caveolin-3 G56S sequence variant of unknown significance: Muscle biopsy findings and functional cell biological analysis
dc.bibliographicCitation.issue | 1-2 | eng |
dc.bibliographicCitation.journalTitle | Proteomics - Clinical Applications | eng |
dc.bibliographicCitation.volume | 11 | |
dc.contributor.author | Brauers, Eva | |
dc.contributor.author | Roos, Andreas | |
dc.contributor.author | Kollipara, Laxmikanth | |
dc.contributor.author | Zahedi, René P. | |
dc.contributor.author | Beckmann, Alf | |
dc.contributor.author | Mohanadas, Nilane | |
dc.contributor.author | Bauer, Hartmut | |
dc.contributor.author | Häusler, Martin | |
dc.contributor.author | Thoma, Stéphanie | |
dc.contributor.author | Kress, Wolfram | |
dc.contributor.author | Senderek, Jan | |
dc.contributor.author | Weis, Joachim | |
dc.date.accessioned | 2018-02-21T22:05:11Z | |
dc.date.available | 2019-06-18T09:00:55Z | |
dc.date.issued | 2016 | |
dc.description.abstract | Purpose: In the era of next-generation sequencing, we are increasingly confronted with se- quence variants of unknown significance. This phenomenon is also known for variations in Caveolin-3 and can complicate the molecular diagnosis of the disease. Here, we aimed to study the ambiguous character of the G56S Caveolin-3 variant. Experimental design: A comprehensive approach combining genetic and morphological stud- ies of muscle derived from carriers of the G56S Caveolin-3 variant were carried out and linked to biochemical assays (including phosphoblot studies and proteome profiling) and morphological investigations of cultured myoblasts. Results: Muscles showed moderate chronic myopathic changes in all carriers of the variant. Myogenic RCMH cells expressing the G56S Caveolin-3 protein presented irregular Caveolin-3 deposits within the Golgi in addition to a regular localization of the protein to the plasma mem- brane. This result was associated with abnormal findings on the ultra-structural level. Phos- phoblot studies revealed that G56S affects EGFR-signaling. Proteomic profiling demonstrated alterations in levels of physiologically relevant proteins which are indicative for antagonization of G56S Caveolin-3 expression. Remarkably, some proteomic alterations were enhanced by osmotic/mechanical stress. Conclusions and clinical relevance: Our studies suggest that G56S might influence the mani- festation of myopathic changes upon the presence of additional cellular stress burden. Results of our studies moreover improve the current understanding of (genetic) causes of myopathic disorders classified as caveolinopathies. | eng |
dc.description.version | publishedVersion | eng |
dc.format | application/pdf | |
dc.identifier.uri | https://doi.org/10.34657/471 | |
dc.identifier.uri | https://oa.tib.eu/renate/handle/123456789/28 | |
dc.language.iso | eng | eng |
dc.publisher | Hoboken, NJ : Wiley | eng |
dc.relation.doi | https://doi.org/10.1002/prca.201600007 | |
dc.rights.license | CC BY-NC-ND 4.0 Unported | eng |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | eng |
dc.subject.ddc | 570 | eng |
dc.subject.other | Caveolin-3 | eng |
dc.subject.other | LGMD-1C | eng |
dc.subject.other | Proteome profile of muscle cells | eng |
dc.subject.other | RCMH | eng |
dc.title | The Caveolin-3 G56S sequence variant of unknown significance: Muscle biopsy findings and functional cell biological analysis | eng |
dc.type | Article | eng |
dc.type | Text | eng |
tib.accessRights | openAccess | eng |
wgl.contributor | ISAS | eng |
wgl.subject | Biowissenschaften/Biologie | eng |
wgl.type | Zeitschriftenartikel | eng |
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