Immunofluorescence-based analysis of caveolin-3 in the diagnostic management of neuromuscular diseases

Abstract

Immunohistochemistry- and/or immunofluorescence-based analysis of muscular proteins represents a standard procedure in the diagnostic management of patients suffering from neuromuscular diseases such as “Caveolinopathies” which are caused by mutations in the CAV3 gene encoding for caveolin-3. Human caveolin-3 is a 151 amino acid sized transmembrane protein localized within caveolae, predominantly expressed in cardiac and skeletal muscle cells and involved in a diversity of cellular functions crucial for muscle cell homeostasis. Loss of caveolin-3 protein abundance is indicative for the presence of pathogenic mutations within the corresponding gene and thus for the diagnosis of “Caveolinopathies.” Moreover, description of abnormal immunoreactivity findings for the caveolin-3 protein is increasing in the context of other neuromuscular diseases suggesting that profound knowledge of abnormal caveolin-3-expression and/or distribution findings can be decisive also for the diagnosis of other neurological diseases as well as for a better understanding of the biology of the protein. Here, we summarize the current knowledge about the caveolin-3, report on a protocol for immunofluorescence-based analysis of the protein in the diagnostic workup of neuromuscular patients—also considering problems encountered—and confirm as well as summarize already published abnormal histological findings in muscular pathologies beyond “Caveolinopathies.”