钙调神经磷酸酶
肌发生
骨骼肌
NFAT公司
心肌细胞
C2C12型
肌生成素
细胞生物学
信号转导
生物
磷酸酶
磷酸化
乌特罗芬
化学
内分泌学
内科学
肌营养不良蛋白
移植
医学
作者
Val A. Fajardo,Colton J. F. Watson,Kirsten N. Bott,Fereshteh Moradi,Lucas A. Maddalena,Catherine A. Bellissimo,Kelli D. Turner,Sandra J. Peters,Paul J. LeBlanc,Adam J. MacNeil,Jeffrey A. Stuart,A. Russell Tupling
出处
期刊:American Journal of Physiology-cell Physiology
[American Physiological Society]
日期:2019-11-01
卷期号:317 (5): C1025-C1033
被引量:12
标识
DOI:10.1152/ajpcell.00345.2018
摘要
Calcineurin is a Ca2+/calmodulin (CaM)-dependent phosphatase that plays a critical role in promoting the slow fiber phenotype and myoblast fusion in skeletal muscle, thereby making calcineurin an attractive cellular target for enhancing fatigue resistance, muscle metabolism, and muscle repair. Neurogranin (Ng) is a CaM-binding protein thought to be expressed solely in brain and neurons, where it inhibits calcineurin signaling by sequestering CaM, thus lowering its cellular availability. Here, we demonstrate for the first time the expression of Ng protein and mRNA in mammalian skeletal muscle. Both protein and mRNA levels are greater in slow-oxidative compared with fast-glycolytic muscles. Coimmunoprecipitation of CaM with Ng in homogenates of C2C12 myotubes, mouse soleus, and human vastus lateralis suggests that these proteins physically interact. To determine whether Ng inhibits calcineurin signaling in muscle, we used Ng siRNA with C2C12 myotubes to reduce Ng protein levels by 60%. As a result of reduced Ng expression, C2C12 myotubes had enhanced CaM-calcineurin binding and calcineurin signaling as indicated by reduced phosphorylation of nuclear factor of activated T cells and increased utrophin mRNA. In addition, calcineurin signaling affects the expression of myogenin and stabilin-2, which are involved in myogenic differentiation and myoblast fusion, respectively. Here, we found that both myogenin and stabilin-2 were significantly elevated by Ng siRNA in C2C12 cells, concomitantly with an increased fusion index. Taken together, these results demonstrate the expression of Ng in mammalian skeletal muscle where it appears to be a novel regulator of calcineurin signaling.
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