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Dysferlin Interacts with Histone Deacetylase 6 and Increases alpha-Tubulin Acetylation

2011· article· en· 39 citations· W1989140603 on OpenAlex· 10.1371/journal.pone.0028563

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Canadian affiliationAn author listed a Canadian institution. This is the only route the usual frame has.
Canadian funderA Canadian agency funded it. The work may carry no Canadian affiliation at all.

Post-publication record

Nature
Retraction
Reason
Falsification/Fabrication of Data;Falsification/Fabrication of Image;Investigation by Company/Institution;
Date
1/29/2018 0:00
Flagged by OpenAlex?
Yes

Source: Retraction Watch, joined by DOI. OpenAlex records retraction as is_retracted, a boolean over a state space with at least four values, so it cannot express an expression of concern, a correction or a reinstatement — it reports them as false, which reads as “fine”.

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

The record

Venue
PLoS ONE
Topic
Histone Deacetylase Inhibitors Research
Field
Biochemistry, Genetics and Molecular Biology
Canadian institutions
McGill UniversityMontreal Neurological Institute and Hospital
Funders
Canadian Institutes of Health ResearchBundesministerium für Bildung und ForschungSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungNational Science Foundation
Keywords
MyogenesisCell biologyDysferlinTubulinAcetylationBiologyMicrotubuleTransmembrane proteinHDAC6NocodazoleHistone deacetylaseChemistryMyocyteHistoneBiochemistryCytoskeletonSkeletal muscleCellReceptorAnatomy
Has abstract in OpenAlex
yes