Sorting of a nonmuscle tropomyosin to a novel cytoskeletal compartment in skeletal muscle results in muscular dystrophy

Anthony J. Kee, Galina Schevzov, Visalini Nair-Shalliker, C. Stephen Robinson, Bernadette Vrhovski, Majid Ghoddusi, Min Ru Qiu, Jim J C Lin, Ron Weinberger, Peter W. Gunning, Edna C. Hardeman*

*Corresponding author for this work

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)685-696
Number of pages12
JournalJournal of Cell Biology
Volume166
Issue number5
DOIs
Publication statusPublished - 30 Aug 2004
Externally publishedYes

Keywords

  • Muscles
  • Muscular dystrophies
  • Sarcomeres
  • Transgenic mice
  • Tropomyosin

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