Di Fulvio, S. and Azakir, B. A. and Therrien, C. and Sinnreich, M.. (2011) Dysferlin interacts with histone deacetylase 6 and increases alpha-tubulin acetylation. PLoS ONE, Vol. 6, H. 12 , e28563.
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Official URL: http://edoc.unibas.ch/dok/A6006575
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Abstract
Dysferlin is a multi-C2 domain transmembrane protein involved in a plethora of cellular functions, most notably in skeletal muscle membrane repair, but also in myogenesis, cellular adhesion and intercellular calcium signaling. We previously showed that dysferlin interacts with alpha-tubulin and microtubules in muscle cells. Microtubules are heavily reorganized during myogenesis to sustain growth and elongation of the nascent muscle fiber. Microtubule function is regulated by post-translational modifications, such as acetylation of its alpha-tubulin subunit, which is modulated by the histone deacetylase 6 (HDAC6) enzyme. In this study, we identified HDAC6 as a novel dysferlin-binding partner. Dysferlin prevents HDAC6 from deacetylating alpha-tubulin by physically binding to both the enzyme, via its C2D domain, and to the substrate, alpha-tubulin, via its C2A and C2B domains. We further show that dysferlin expression promotes alpha-tubulin acetylation, as well as increased microtubule resistance to, and recovery from, Nocodazole- and cold-induced depolymerization. By selectively inhibiting HDAC6 using Tubastatin A, we demonstrate that myotube formation was impaired when alpha-tubulin was hyperacetylated early in the myogenic process; however, myotube elongation occurred when alpha-tubulin was hyperacetylated in myotubes. This study suggests a novel role for dysferlin in myogenesis and identifies HDAC6 as a novel dysferlin-interacting protein.
Faculties and Departments: | 03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Neuromuscular Research (Sinnreich) |
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UniBasel Contributors: | Sinnreich, Michael |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
Publisher: | Public Library of Science |
e-ISSN: | 1932-6203 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Related URLs: | |
Identification Number: |
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Last Modified: | 31 Aug 2018 06:40 |
Deposited On: | 27 Feb 2014 15:45 |
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