title: alpha-Skeletal muscle actin mutants causing different congenital myopathies induce similar cytoskeletal defects in cell line cultures.
abstract: 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 in 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.
authors.affiliation: Department for Medical Protein Research, VIB, Gent University, A. Baertsoenkaai 3, Gent, Belgium.
authors.forename: Drieke
authors.initials: D
authors.lastname: Vandamme
authors.forename: Heidi
authors.initials: H
authors.lastname: Rommelaere
authors.forename: Ellen
authors.initials: E
authors.lastname: Lambert
authors.forename: Davy
authors.initials: D
authors.lastname: Waterschoot
authors.forename: Joël
authors.initials: J
authors.lastname: Vandekerckhove
authors.forename: Bruno
authors.initials: B
authors.lastname: Constantin
authors.forename: Christophe
authors.initials: C
authors.lastname: Ampe
mesh_terms: D000199:Actins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology; D032446:Myoblasts / Q000378:metabolism; D017696:Myopathies, Nemaline / Q000235:genetics / Q000378:metabolism; D020914:Myopathies, Structural, Congenital / Q000235:genetics* / Q000378:metabolism; D020512:Myopathy, Central Core / Q000235:genetics* / Q000378:metabolism; D041681:NIH 3T3 Cells; D011487:Protein Conformation; D017510:Protein Folding; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism
chemical_list: D000199:Actins; D019837:Ryanodine Receptor Calcium Release Channel