Phenotypes induced by NM causing alpha-skeletal muscle actin mutants in fibroblasts, Sol 8 myoblasts and myotubes.
BACKGROUND
Nemaline myopathy is a neuromuscular disorder characterized by the presence of nemaline bodies in patient muscles. 20% of the cases are associated with alpha-skeletal muscle actin mutations. We previously showed that actin mutations can cause four different biochemical phenotypes and that expression of NM associated actin mutants in fibroblasts, myoblasts and myotubes induces a range of cellular defects.


RESULTS
We conducted the same biochemical experiments for twelve new actin mutants associated with nemaline myopathy. We observed folding and polymerization defects. Immunostainings of these and eight other mutants in transfected cells revealed typical cellular defects such as nemaline rods or aggregates, decreased incorporation in F-actin structures, membrane blebbing, the formation of thickened actin fibres and cell membrane blebbing in myotubes.


CONCLUSIONS
Our results confirm that NM associated alpha-actin mutations induce a range of defects at the biochemical level as well as in cultured fibroblasts and muscle cells.
Vandamme
Drieke
D
Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, A, Baertsoenkaai 3, Gent, Belgium. drieke.vandamme@ugent.be
Lambert
Ellen
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Waterschoot
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Tondeleir
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Vandekerckhove
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Machesky
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Constantin
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Rommelaere
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Ampe
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