alpha-Skeletal Muscle Actin Mutants Causing Different Congenital Myopathies Induce Similar Cytoskeletal Defects in Cell Line Cultures

作者：Vandamme Drieke; Rommelaere Heidi; Lambert Ellen; Waterschoot Davy; Vandekerckhove Joel; Constantin Bruno; Ampe Christophe^*

来源：Cell Motility and the Cytoskeleton, 2009, 66(4): 179-192.

DOI：10.1002/cm.20340

• alpha-actin mutation
• central core disease
• congenital fibre type disproportion
• nemaline myopathy
• muscle cells

Central core disease (CCD), congenital fibre type disproportion (CFTD), and nemaline myopathy (NM) are earlyonset clinically heterogeneous congenital myopathies, characterized by generalized Muscle weakness and hypotonia. All three diseases are associated with (alpha-skeletal muscle actin mutations. We biochemically characterized the CCD and CFTD causing actin mutants and show that all Mutants fold correctly and are stable. Expression studies in fibroblasts, myoblasts, and myotubes show that these mutants incorporate in filamentous structures. However they do not intercalate between the nascent z-lines it) differentiating muscle cell Cultures. We also show that the distribution of mitochondria and of the ryanodine receptors, and calcium release properties from ryanodine receptors, are unchanged in myotubes expressing the CCD causing mutants. CFTD causing mutants induce partly similar phenotypes as NM associated ones, such as rods and thickened actin fibers in cell Culture. Our results, Suggest that molecular mechanisms behind CFTD and NM may be partly related. Cell Motil. Cytoskeleton 66: 179-192, 2009.

• 出版日期2009-4