2004/08/30 by Anthony J. Kee, Galina Schevzov, Visalini Nair‐Shalliker +8 · 2 citations
Biochemistry, Genetics and Molecular Biology · Medicine · Neuroscience · #Muscle Physiology and Disorders #Cardiomyopathy and Myosin Studies #Genetic Neurodegenerative Diseases #Tropomyosin #Sarcomere #Biology #Gene isoform #Cytoskeleton #Actin #Skeletal muscle #Cell biology #Muscular dystrophy #Actinin #Ankyrin #Anatomy #Spectrin #Intermediate filament #ITGA7 #Myosin #Myofibril #Myocyte #Biochemistry #Genetics #Gene #Cell
paper · pdf · doi:10.1083/jcb.200406181
openalex publication_date 2004/08/30 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/11
Tropomyosin (Tm) is a key component of the actin cytoskeleton and >40 isoforms have been described in mammals. In addition to the isoforms in the sarcomere, we now report the existence of two nonsarcomeric (NS) isoforms in skeletal muscle. These isoforms are excluded from the thin filament of the sarcomere and are localized to a novel Z-line adjacent structure. Immunostained cross sections indicate that one Tm defines a Z-line adjacent structure common to all myofibers, whereas the second Tm defines a spatially distinct structure unique to muscles that undergo chronic or repetitive contractions. When a Tm (Tm3) that is normally absent from muscle was expressed in mice it became associated with the Z-line adjacent structure. These mice display a muscular dystrophy and ragged-red fiber phenotype, suggestive of disruption of the membrane-associated cytoskeletal network. Our findings raise the possibility that mutations in these tropomyosin and these structures may underpin these types of myopathies.