Global O-GlcNAcylation changes impact desmin phosphorylation and its partition toward cytoskeleton in C2C12 skeletal muscle cells differentiated into myotubes

Claeyssen, Charlotte; Bastide, Bruno; Cieniewski-Bernard, Caroline

doi:10.1038/s41598-022-14033-z

Cited by 8 publications

(1 citation statement)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The supernatant or cytosolic desmin pool, being detergent-soluble, might undergo post-translational modi cations that hinder antibody binding. Desmin is known to undergo various PTMs [68], such as ubiquitination [16] or, as recently shown O-GlcNAcylation [14]. Interestingly, the latter occurs exclusively in the nucleus and cytosol [29], which could explain another phenomenon we observed: The antibody against p Des S60 produced a band slightly higher than predicted or than the total protein (Fig.…”

Section: Resultssupporting

confidence: 62%

Desmin Phosphorylation in human skeletal muscle can be modified by Resistance Exercise rendering the protein less vulnerable to protease-dependent cleavage

Jacko,

Schaaf,

Aussieker

et al. 2024

Preprint

View full text Add to dashboard Cite

The desmin intermediate filament (IF) system plays a crucial role in stress transmission, mechano-protection, and the regulation of signaling in skeletal muscle. Loss of IF integrity is considered a triggering factor for myofibril breakdown and muscle atrophy. Phosphorylation of desmin (pDes) has been identified as a priming factor leading to an organized process provoking muscle atrophy. Intervening in pDes has been suggested as a promising method to counteract the loss of muscle mass. Physical exercise stands out as a prominent and non-pharmacological option for purposefully modifying cellular signaling to promote muscle health and function. To investigate whether resistance exercise (RE) specifically influences the regulation of pDes, 10 healthy young men (n=7) and women (n=3) performed 7 weeks of RE training (14 sessions; 2 per week). Muscle biopsies were collected in both untrained and trained conditions at rest (pre 1, pre 14) and one hour after RE (post 1, post 14). Desmin content and phosphorylation at serine 31 and 60 (pDesS31, pDesS60) as well as threonine 17 and 76/77 (pDesT17, pDesT76/77) were analyzed. In untrained condition (pre 1, post 1), acute RE resulted in the dephosphorylation of S31 (p < 0.001) and S60 (p < 0.05). This was accompanied by reduced susceptibility of desmin in the exercised muscle to protease-induced cleavage compared to the resting state (p < 0.05). In the trained condition (pre 14, post 14), acute RE led to an augmented dephosphorylation of S31 (p < 0.01) as compared to the untrained condition (p < 0.05). Furthermore, training affected baseline phosphorylation, upregulating S31 and attenuating S60 as well as T17 while increasing total desmin content. We conclude that RE is a potent stimulus for modifying desmin phosphorylation, making the protein less prone to cleavage. Because repeated resistance training changes the phosphorylation pattern of Desmin, we introduce pDes as an adaptive mechanism of skeletal muscle, contributing to the proteostatic regulation in response to recurring stress. Focusing on underlying mechanisms and determining the most effective loading in RE-dependent induction of pDes-modification might be a promising strategy to challenge muscle atrophy in health and disease.

show abstract

Section: Resultssupporting

confidence: 62%

Desmin Phosphorylation in human skeletal muscle can be modified by Resistance Exercise rendering the protein less vulnerable to protease-dependent cleavage

Jacko,

Schaaf,

Aussieker

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

A novel 2D‐electrophoresis method for the simultaneous visualization of phosphorylated and O‐GlcNAcylated proteoforms of a protein

Bulangalire,

Claeyssen,

Douffi

et al. 2024

Electrophoresis

View full text Add to dashboard Cite

Post‐translational modifications (PTMs), such as phosphorylation and O‐N‐acetyl‐β‐d‐glucosaminylation (O‐GlcNAcylation), are involved in the fine spatiotemporal regulation of protein functions, and their dynamic interplay is at the heart of protein language. The coexistence of phosphorylation and O‐GlcNAcylation on a protein leads to the diversification of proteoforms. It is therefore essential to decipher the phosphorylation/O‐GlcNAcylation interplay on protein species that orchestrates cellular processes in a specific physiological or pathophysiological context. However, simultaneous visualization of phosphorylation and O‐GlcNAcylation patterns on a protein of interest remains a challenge. To map the proteoforms of a protein, we have developed an easy‐to‐use two‐dimensional electrophoresis method with a single sample processing permitting simultaneous visualization of the phosphorylated and the O‐GlcNAcylated forms of the protein of interest. This method, we termed 2D‐WGA‐Phos‐tag‐PAGE relies on proteoforms retardation by affinity gel electrophoresis. With this novel approach, we established the cartography of phospho‐ and glycoforms of αB‐crystallin and desmin in the whole extract and the cytoskeleton protein subfraction in skeletal muscle cells. Interestingly, we have shown that the pattern of phosphorylation and O‐GlcNAcylation depends of the subcellular subfraction. Moreover, we have also shown that proteotoxic stress condition increased the complexity of the pattern of PTMs on αB‐crystallin.

show abstract

Desmin and its molecular chaperone, the αB-crystallin: How post-translational modifications modulate their functions in heart and skeletal muscles?

Claeyssen,

Bulangalire,

Bastide

et al. 2024

Biochimie

View full text Add to dashboard Cite

Global O-GlcNAcylation changes impact desmin phosphorylation and its partition toward cytoskeleton in C2C12 skeletal muscle cells differentiated into myotubes

Cited by 8 publications

References 74 publications

Desmin Phosphorylation in human skeletal muscle can be modified by Resistance Exercise rendering the protein less vulnerable to protease-dependent cleavage

Desmin Phosphorylation in human skeletal muscle can be modified by Resistance Exercise rendering the protein less vulnerable to protease-dependent cleavage

A novel 2D‐electrophoresis method for the simultaneous visualization of phosphorylated and O‐GlcNAcylated proteoforms of a protein

Desmin and its molecular chaperone, the αB-crystallin: How post-translational modifications modulate their functions in heart and skeletal muscles?

Contact Info

Product

Resources

About