The Phosphorylation Profile of Myosin Binding Protein-C Slow is Dynamically Regulated in Slow-Twitch Muscles in Health and Disease.
Myosin Binding Protein-C slow (sMyBP-C) is expressed in skeletal muscles where it plays structural and regulatory roles. The functions of sMyBP-C are modulated through alternative splicing and phosphorylation. Herein, we examined the phosphorylation profile of sMyBP-C in mouse slow-twitch soleus muscle isolated from fatigued or non-fatigued young (2-4-months old) and old (~14-months old) wild type and mdx mice. Our findings are two-fold. First, we identified the phosphorylation events present in individual sMyBP-C variants at different states. Secondly, we quantified the relative abundance of each phosphorylation event, and of sMyBP-C phospho-species as a function of age and dystrophy, in the presence or absence of fatigue. Our results revealed both constitutive and differential phosphorylation of sMyBP-C. Moreover, we noted a 10-40% and a 25-35% reduction in the phosphorylation levels of select sites in old wild type and young or old mdx soleus muscles, respectively. On the contrary, we observed a 5-10% and a 20-25% increase in the phosphorylation levels of specific sites in young fatigued wild type and mdx soleus muscles, respectively. Overall, our studies showed that the phosphorylation pattern of sMyBP-C is differentially regulated following reversible (i.e. fatigue) and non-reversible (i.e. age and disease) (patho)physiological stressors.
University of Maryland, School of Medicine, Department of Biochemistry and Molecular Biology, Baltimore, MD, USA.
Maegen A
MA
Ackermann
University of Maryland, School of Medicine, Department of Physiology, Baltimore, MD, USA.
Jaclyn P
JP
Kerr
University of Maryland, School of Medicine, Department of Biochemistry and Molecular Biology, Baltimore, MD, USA.
Brendan
B
King
University of Maryland, School of Nursing, Baltimore, MD, USA.
Christopher
C
W Ward
University of Maryland, School of Medicine, Department of Biochemistry and Molecular Biology, Baltimore, MD, USA.
Aikaterini
A
Kontrogianni-Konstantopoulos
D020816:Amino Acid Motifs; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018763:Muscle Fatigue; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism*; D009135:Muscular Diseases / Q000378:metabolism* / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D000099163:Myosin Binding Protein C
D002352:Carrier Proteins; D000099163:Myosin Binding Protein C