Deng Yu Feng, Huang Yi Yuan, Lu Wen Sheng, Huang Yuan Heng, Xian Jing, Wei Hong Qiao, Huang Qin
School of Nursing, Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Department of Endocrinology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.
Biochem Biophys Res Commun. 2017 Apr 29;486(2):218-223. doi: 10.1016/j.bbrc.2017.02.072. Epub 2017 Feb 21.
Caveolin-3 (CAV3) is a muscle specific protein that plays an important role in maintaining muscle health and glucose homeostasis in vivo. A novel autosomal dominant form of LGMD-1C in humans is due to a P104L mutation within the coding sequence of the human CAV3 gene. The mechanism by which the LGMD-1C mutation leads to muscle weakness remains unknown. Our objective was to determine whether muscle weakness was related to the imbalance of glucose metabolism. We found that when the P104L mutation was transiently transfected into C2C12 cells, there was decreased glucose uptake and glycogen synthesis after insulin stimulation. Immunoblotting analysis showed that the P104L mutation resulted in decreased expression of CAV3, CAV1 and pAkt. Confocal immunomicroscopy indicated that the P104L mutation reduced CAV3 and GLUT4 in the cell membrane, which accumulated mainly near the nucleus. This work is the first report of an association between muscle weakness due to LGMD-1C and energy metabolism. The P104L mutation led to a decrease in C2C12 muscle glucose uptake and glycogen synthesis and may be involved in the pathogenesis of LGMD-1C.
小窝蛋白-3（CAV3）是一种肌肉特异性蛋白，在维持体内肌肉健康和葡萄糖稳态方面发挥着重要作用。人类一种新的常染色体显性形式的LGMD-1C是由于人类CAV3基因编码序列中的P104L突变所致。LGMD-1C突变导致肌肉无力的机制尚不清楚。我们的目标是确定肌肉无力是否与葡萄糖代谢失衡有关。我们发现，当将P104L突变瞬时转染到C2C12细胞中时，胰岛素刺激后葡萄糖摄取和糖原合成减少。免疫印迹分析表明，P104L突变导致CAV3、CAV1和pAkt表达降低。共聚焦免疫显微镜检查表明，P104L突变减少了细胞膜中的CAV3和GLUT4，它们主要聚集在细胞核附近。这项工作是关于LGMD-1C所致肌肉无力与能量代谢之间关联的首次报道。P104L突变导致C2C12肌肉葡萄糖摄取和糖原合成减少，可能参与了LGMD-1C的发病机制。
