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Phospho-GlcNAc modulation of slow MLC2 during soleus atrophy through a multienzymatic and sarcomeric complex.
Pflugers Arch. 2014 Nov; 466(11):2139-51.PA

Abstract

Although calcium is the major regulator of excitation-contraction coupling, myofilament function can also be modulated through post-translational modifications. In particular, phosphorylation and O-GlcNAcylation are key modulators of calcium activation parameters. Among the regulatory proteins of skeletal muscle contraction, the myosin light chain 2 (MLC2) can undergo both types of post-translational modification. During aging or physical inactivity, the phosphorylation status of the slow isoform of MLC2 (sMLC2) does not correlate with calcium sensitivity, suggesting that the O-GlcNAcylation might modulate sMLC2 activity. To increase understanding of the contractile dysfunction associated with muscle atrophy, we studied the phosphorylation/O-GlcNAcylation interplay on the sMLC2. We demonstrate a two-fold decrease of O-GlcNAcylation level on sMLC2 in a rat model of skeletal muscle atrophy (hindlimb unloading), while phosphorylation increased. Both post-translational modifications were mutually exclusive. Their interplay reversed during reloading. The expression of enzymes involved in the phosphorylation and O-GlcNAcylation interplay on sMLC2 was modified on whole protein pattern as well as on myofilament, and was load-dependent. All enzymes were colocalized on the contractile apparatus. Finally, we describe a multienzymatic complex which might finely modulate the phosphorylation/dephosphorylation and O-GlcNAcylation/de-O-GlcNAcylation of sMLC2 that could be involved in the contractile dysfunction of atrophied muscle. Importantly, this complex was localized at the Z-disk, a nodal point of signalling in skeletal muscle.

Authors+Show Affiliations

Université Lille Nord de France, Université de Lille 1, Villeneuve d'Ascq, France, caroline.cieniewski-bernard@univ-lille1.fr.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24477671

Citation

Cieniewski-Bernard, Caroline, et al. "Phospho-GlcNAc Modulation of Slow MLC2 During Soleus Atrophy Through a Multienzymatic and Sarcomeric Complex." Pflugers Archiv : European Journal of Physiology, vol. 466, no. 11, 2014, pp. 2139-51.
Cieniewski-Bernard C, Dupont E, Richard E, et al. Phospho-GlcNAc modulation of slow MLC2 during soleus atrophy through a multienzymatic and sarcomeric complex. Pflugers Arch. 2014;466(11):2139-51.
Cieniewski-Bernard, C., Dupont, E., Richard, E., & Bastide, B. (2014). Phospho-GlcNAc modulation of slow MLC2 during soleus atrophy through a multienzymatic and sarcomeric complex. Pflugers Archiv : European Journal of Physiology, 466(11), 2139-51. https://doi.org/10.1007/s00424-014-1453-y
Cieniewski-Bernard C, et al. Phospho-GlcNAc Modulation of Slow MLC2 During Soleus Atrophy Through a Multienzymatic and Sarcomeric Complex. Pflugers Arch. 2014;466(11):2139-51. PubMed PMID: 24477671.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phospho-GlcNAc modulation of slow MLC2 during soleus atrophy through a multienzymatic and sarcomeric complex. AU - Cieniewski-Bernard,Caroline, AU - Dupont,Erwan, AU - Richard,Elodie, AU - Bastide,Bruno, Y1 - 2014/01/30/ PY - 2013/07/15/received PY - 2014/01/15/accepted PY - 2014/01/14/revised PY - 2014/1/31/entrez PY - 2014/1/31/pubmed PY - 2015/6/24/medline SP - 2139 EP - 51 JF - Pflugers Archiv : European journal of physiology JO - Pflugers Arch VL - 466 IS - 11 N2 - Although calcium is the major regulator of excitation-contraction coupling, myofilament function can also be modulated through post-translational modifications. In particular, phosphorylation and O-GlcNAcylation are key modulators of calcium activation parameters. Among the regulatory proteins of skeletal muscle contraction, the myosin light chain 2 (MLC2) can undergo both types of post-translational modification. During aging or physical inactivity, the phosphorylation status of the slow isoform of MLC2 (sMLC2) does not correlate with calcium sensitivity, suggesting that the O-GlcNAcylation might modulate sMLC2 activity. To increase understanding of the contractile dysfunction associated with muscle atrophy, we studied the phosphorylation/O-GlcNAcylation interplay on the sMLC2. We demonstrate a two-fold decrease of O-GlcNAcylation level on sMLC2 in a rat model of skeletal muscle atrophy (hindlimb unloading), while phosphorylation increased. Both post-translational modifications were mutually exclusive. Their interplay reversed during reloading. The expression of enzymes involved in the phosphorylation and O-GlcNAcylation interplay on sMLC2 was modified on whole protein pattern as well as on myofilament, and was load-dependent. All enzymes were colocalized on the contractile apparatus. Finally, we describe a multienzymatic complex which might finely modulate the phosphorylation/dephosphorylation and O-GlcNAcylation/de-O-GlcNAcylation of sMLC2 that could be involved in the contractile dysfunction of atrophied muscle. Importantly, this complex was localized at the Z-disk, a nodal point of signalling in skeletal muscle. SN - 1432-2013 UR - https://www.unboundmedicine.com/medline/citation/24477671/Phospho_GlcNAc_modulation_of_slow_MLC2_during_soleus_atrophy_through_a_multienzymatic_and_sarcomeric_complex_ L2 - https://dx.doi.org/10.1007/s00424-014-1453-y DB - PRIME DP - Unbound Medicine ER -