期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
卷 1860, 期 9, 页码 2017-2030出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagen.2016.06.011
关键词
Sarcomere structure; Skeletal muscle cells; O-GlcNAcylation; Protein-protein interactions; Desmin; alpha B-crystallin
资金
- Region Nord-Pas-de-Calais (Emergent Research Project) [12003803]
- Centre National d'Etudes Spatiales [4800000784]
Background: The sarcomere structure of skeletal muscle is determined through multiple protein protein interactions within an intricate sarcomeric cytoskeleton network. The molecular mechanisms involved in the regulation of this sarcomeric organization, essential to muscle function, remain unclear. O-GlcNAcylation, a post translational modification modifying several key structural proteins and previously described as a modulator of the contractile activity, was never considered to date in the sarcomeric organization. Methods: C2C12 skeletal myotubes were treated with Thiamet-G (OGA inhibitor) in order to increase the global O-GlcNAcylation level. Results: Our data clearly showed a modulation of the O-GlcNAc level more sensitive and dynamic in the myofilament-enriched fraction than total proteome. This fine O-GlcNAc level modulation was closely related to changes of the sarcomeric morphometry. Indeed, the dark-band and M-line widths increased, while the I-band width and the sarcomere length decreased according to the myofilament O-GlcNAc level. Some structural proteins of the sarcomere such as desmin, alpha B-crystallin, alpha-actinin, moesin and filamin-C have been identified within modulated protein complexes through O-GlcNAc level variations. Their interactions seemed to be changed, especially for desmin and alpha B-crystallin. Conclusions: For the first time, our findings clearly demonstrate that O-GlcNAcylation, through dynamic regulations of the structural interactome, could be an important modulator of the sarcomeric structure and may provide new insights in the understanding of molecular mechanisms of neuromuscular diseases characterized by a disorganization of the sarcomeric structure. General significance: In the present study, we demonstrated a role of O-GlcNAcylation in the sarcomeric structure modulation. (C) 2016 Elsevier B.V. All rights reserved.
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