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Posttranslational modifications of desmin and their implication in biological processes and pathologies

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Abstract

Desmin, the muscle-specific intermediate filament, is involved in myofibrillar myopathies, dilated cardiomyopathy and muscle wasting. Desmin is the target of posttranslational modifications (PTMs) such as phosphorylation, ADP-ribosylation and ubiquitylation as well as nonenzymatic modifications such as glycation, oxidation and nitration. Several PTM target residues and their corresponding modifying enzymes have been discovered in human and nonhuman desmin. The major effect of phosphorylation and ADP-ribosylation is the disassembly of desmin filaments, while ubiquitylation of desmin leads to its degradation. The regulation of the desmin filament network by phosphorylation and ADP-ribosylation was found to be implicated in several major biological processes such as myogenesis, myoblast fusion, muscle contraction, muscle atrophy, cell division and possibly desmin interactions with its binding partners. Phosphorylation of desmin is also implicated in many forms of desmin-related myopathies (desminopathies). In this review, we summarize the findings on desmin PTMs and their implication in biological processes and pathologies, and discuss the current knowledge on the regulation of the desmin network by PTMs. We conclude that the desmin filament network can be seen as an intricate scaffold for muscle cell structure and biological processes and that its dynamics can be affected by PTMs. There are now precise tools to investigate PTMs and visualize cellular structures that have been underexploited in the study of desminopathies. Future studies should focus on these aspects.

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Abbreviations

ADPRH:

ADP-ribosylarginine hydrolase

AGE:

Advanced glycation end product

AKAP:

A-kinase anchoring protein

ART:

Mono-ADP-ribosyltransferase

Aurora-B:

Aurora kinase B

Br-8-cAMP:

8-Bromo-cAMP

CaMKII:

Ca2+/calmodulin-dependent protein kinase II

CDK:

Cyclin-dependent kinase

CEL:

N-carboxyethyl-lysine

CML:

N-carboxymethyl-lysine

HNE:

4-Hydroxynonenal

IF:

Intermediate filament

MDAL:

Malondialdehyde-lysine

MFM:

Myofibrillar myopathy

N-tyr:

Nitrotyrosine

PAK:

p21-activated kinase

PKA:

Protein kinase A

PKC:

Protein kinase C

PLB:

Phospholamban

PP1:

Type 1 protein phosphatase

PTMs:

Posttranslational modifications

Rho-kinase:

Rho-associated kinase

T3:

Triiodothyronine

TRIM32:

E3 ubiquitin-protein ligase TRIM32

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Acknowledgments

We would like to thank Dr. Baraibar MA, Dr. Parlakian A, Dr. Pinet F, Pr. Agbulut O and Pr. Foulon T for fruitful discussions. The work was supported by the Association Française contre les Myopathies (AFM) and the Université Pierre et Marie Curie Paris 6 (UPMC). The authors are grateful to colleagues for their contribution in the field and apologize to those works that we were unable to cite owing to lack of space.

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No conflicts of interest, financial or otherwise, are declared by the authors.

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  1. Department of Aging, Stress and Inflammation, Université Pierre et Marie Curie (Univ Paris 6), Sorbonne Universités, Paris, France

    Daniel L. Winter, Denise Paulin, Mathias Mericskay & Zhenlin Li

  2. UR4, Vieillissement, Stress and Inflammation, Université Pierre et Marie Curie, 7 quai Saint Bernard, 75252, Paris Cedex 05, France

    Zhenlin Li

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  1. Daniel L. Winter
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Correspondence to Zhenlin Li.

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Daniel L. Winter, Denise Paulin, Mathias Mericskay and Zhenlin Li have equally contributed to the final manuscript.

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Winter, D.L., Paulin, D., Mericskay, M. et al. Posttranslational modifications of desmin and their implication in biological processes and pathologies. Histochem Cell Biol 141, 1–16 (2014). https://doi.org/10.1007/s00418-013-1148-z

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