title: The Caveolin-3 P104L mutation of LGMD-1C leads to disordered glucose metabolism in muscle cells.
abstract: 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.
authors.affiliation: School of Nursing, Youjiang Medical University for Nationalities, Baise, Guangxi, China.
authors.forename: Yu Feng
authors.initials: YF
authors.lastname: Deng
authors.affiliation: School of Nursing, Youjiang Medical University for Nationalities, Baise, Guangxi, China.
authors.forename: Yi Yuan
authors.initials: YY
authors.lastname: Huang
authors.affiliation: Department of Endocrinology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.
authors.forename: Wen Sheng
authors.initials: WS
authors.lastname: Lu
authors.affiliation: Department of Physiology, Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Yuan Heng
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xian
authors.affiliation: Department of Physiology, Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Hong Qiao
authors.initials: HQ
authors.lastname: Wei
authors.affiliation: Department of Physiology, Guangxi Medical University, Nanning, Guangxi, China. Electronic address: hqgxmu@163.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D051244:Caveolin 3 / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics* / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics / Q000473:pathology; D009154:Mutation; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D017433:Protein Structure, Secondary; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019076:Transgenes
chemical_list: C495541:Cav1 protein, mouse; C495548:Cav3 protein, mouse; D051242:Caveolin 1; D051244:Caveolin 3; D051275:Glucose Transporter Type 4; D007328:Insulin; C495693:Slc2a4 protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D006003:Glycogen; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
keywords: Caveolin; Glucose metabolism; Glycogen; Insulin; Muscular dystrophies