O-linked N-acetylglucosaminylation is involved in the Ca2+ activation properties of rat skeletal muscle.
O-Linked N-acetylglucosaminylation termed O-GlcNAc is a dynamic cytosolic and nuclear glycosylation that is dependent both on glucose flow through the hexosamine biosynthesis pathway and on phosphorylation because of the existence of a balance between phosphorylation and O-GlcNAc. This glycosylation is a ubiquitous post-translational modification, which probably plays an important role in many aspects of protein functions. We have previously reported that, in skeletal muscle, proteins of the glycolytic pathway, energetic metabolism, and contractile proteins were O-GlcNAc-modified and that O-Glc-NAc variations could control the muscle protein homeostasis and be implicated in the regulation of muscular atrophy. In this paper, we report O-N-acetylglucosaminylation of a number of key contractile proteins (i.e. myosin heavy and light chains and actin), which suggests that this glycosylation could be involved in skeletal muscle contraction. Moreover, our results showed that incubation of skeletal muscle skinned fibers in N-acetyl-d-glucosamine, in a concentration solution known to inhibit O-GlcNAc-dependent interactions, induced a decrease in calcium sensitivity and affinity of muscular fibers, whereas the cooperativity of the thin filament proteins was not modified. Thus, our results suggest that O-GlcNAc is involved in contractile protein interactions and could thereby modulate muscle contraction.
Hedou
Julie
J
Laboratoire de Plasticité Neuromusculaire, Unité de Neurosciences et Physiologie Adaptatives, UPRES EA 4052, 59655 Villeneuve d'Ascq Cedex, France.
Cieniewski-Bernard
Caroline
C
Leroy
Yves
Y
Michalski
Jean-Claude
JC
Mounier
Yvonne
Y
Bastide
Bruno
B
D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology*; D006031:Glycosylation; D006706:Homeostasis / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009133:Muscular Atrophy / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D009124:Muscle Proteins; D002118:Calcium; D000117:Acetylglucosamine