Beta-tropomyosin mutations alter tropomyosin isoform composition.
OBJECTIVE
Tropomyosin (TM) is an actin-binding protein, which is localized head to tail along the length of the actin filament. There are three major TM isoforms in human striated muscle. Mutations in beta-tropomyosin (TPM2) have recently been identified as an important cause of neuromuscular disorders.


METHODS
The expression of TM isoforms in patients carrying mutations in TPM2 was detected using a combination of SDS-PAGE, Western blotting, and a new method to measure the relative abundance of the various TM transcripts.


RESULTS
The level of gamma-TM is reduced in patients with mutations in TPM2. Beta-tropomyosin was expressed at high levels in muscle specimens of the patients.


CONCLUSIONS
Our study indicates that beta-TM gene mutations can alter the expression of other sarcomeric TM isoforms and that the perturbation of TM isoform levels may affect the dimer preference within the thin filaments, which may contribute to muscle weakness as a result of both functional and structural changes in muscle.
Nilsson
J
J
Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden.
Tajsharghi
H
H
D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000502:physiology*; D009154:Mutation; D020033:Protein Isoforms / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020539:Sequence Analysis, Protein; D014335:Tropomyosin / Q000096:biosynthesis* / Q000235:genetics*
D020033:Protein Isoforms; D012333:RNA, Messenger; D014335:Tropomyosin