Department of Paediatrics, Muscular and Neurodegenerative Disease Unit, University of Genova, G. Gaslini Institute, Genova, Italy.
Eur J Hum Genet. 2010 Feb;18(2):137-45. doi: 10.1038/ejhg.2009.103. Epub 2009 Jul 8.
In muscle tissue the protein caveolin-3 forms caveolae--flask-shaped invaginations localized on the cytoplasmic surface of the sarcolemmal membrane. Caveolae have a key role in the maintenance of plasma membrane integrity and in the processes of vesicular trafficking and signal transduction. Mutations in the caveolin-3 gene lead to skeletal muscle pathology through multiple pathogenetic mechanisms. Indeed, caveolin-3 deficiency is associated to sarcolemmal membrane alterations, disorganization of skeletal muscle T-tubule network and disruption of distinct cell-signaling pathways. To date, there have been 30 caveolin-3 mutations identified in the human population. Caveolin-3 defects lead to four distinct skeletal muscle disease phenotypes: limb girdle muscular dystrophy, rippling muscle disease, distal myopathy, and hyperCKemia. In addition, one caveolin-3 mutant has been described in a case of hypertrophic cardiomyopathy. Many patients show an overlap of these symptoms and the same mutation can be linked to different clinical phenotypes. This variability can be related to additional genetic or environmental factors. This review will address caveolin-3 biological functions in muscle cells and will describe the muscle and heart disease phenotypes associated with caveolin-3 mutations.
在肌肉组织中，蛋白质 caveolin-3 形成 caveolae——位于质膜细胞质表面的烧瓶状凹陷。Caveolae 在维持质膜完整性以及囊泡运输和信号转导过程中起着关键作用。Caveolin-3 基因突变通过多种发病机制导致骨骼肌病变。事实上，caveolin-3 缺乏与质膜改变、骨骼肌 T 小管网络的紊乱以及不同细胞信号通路的破坏有关。迄今为止，在人类中已经发现了 30 种 caveolin-3 突变。Caveolin-3 缺陷导致四种不同的骨骼肌疾病表型：肢带型肌营养不良症、波纹肌病、远端肌病和高肌酸激酶血症。此外，在一例肥厚型心肌病中还描述了一种 caveolin-3 突变体。许多患者表现出这些症状的重叠，并且相同的突变可以与不同的临床表型相关。这种可变性可能与其他遗传或环境因素有关。这篇综述将讨论 caveolin-3 在肌肉细胞中的生物学功能，并描述与 caveolin-3 突变相关的肌肉和心脏病表型。
