Facioscapulohumeral muscular dystrophy region gene-1 (FRG-1) is an actin-bundling protein associated with muscle-attachment sites

Qian Liu, Takako Iida Jones, Vivian W. Tang, William M. Brieher, Peter L. Jones

Research output: Contribution to journalArticle

Abstract

In vertebrates, overexpression of facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) recapitulates the pathophysiology exhibited by FSHD patients, although the role of FRG1 in FSHD remains controversial and no precise function for FRG1 has been described in any organism. To gain insight into the function and potential role of FRG1 in FSHD, we analyzed the highly conserved Caenorhabditis elegans ortholog, frg-1. C. elegans body-wall muscles contain two distinct subcellular pools of FRG-1: nuclear FRG-1, concentrated in the nucleoli; and cytoplasmic FRG-1, associated with the Z-disk and costamere-like structures known as dense bodies. Functionally, we demonstrate that FRG-1 is an F-actin-bundling protein, consistent with its localization to dense bodies; this activity is conserved in human FRG1. This is particularly intriguing because it places FRG-1 along side the list of densebody components whose vertebrate orthologs are involved in the myriad myopathies associated with disrupted costameres and Z-disks. Interestingly, overexpressed FRG-1 preferentially accumulates in the nucleus and, when overexpressed specifically from the frg-1 promoter, disrupts the adult ventral muscle structure and organization. Together, these data further support a role for FRG1 overexpression in FSHD pathophysiology and reveal the previously unsuspected direct involvement of FRG-1 in muscle structure and integrity.

Original languageEnglish (US)
Pages (from-to)1116-1123
Number of pages8
JournalJournal of cell science
Volume123
Issue number7
DOIs
StatePublished - Apr 1 2010

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Facioscapulohumeral Muscular Dystrophy
Actins
Muscles
Genes
Proteins
Costameres
Caenorhabditis elegans
Vertebrates
Muscular Diseases

Keywords

  • Actin
  • Dense body
  • FRG1
  • FSHD
  • Muscle
  • Muscular dystrophy

ASJC Scopus subject areas

  • Cell Biology

Cite this

Facioscapulohumeral muscular dystrophy region gene-1 (FRG-1) is an actin-bundling protein associated with muscle-attachment sites. / Liu, Qian; Jones, Takako Iida; Tang, Vivian W.; Brieher, William M.; Jones, Peter L.

In: Journal of cell science, Vol. 123, No. 7, 01.04.2010, p. 1116-1123.

Research output: Contribution to journalArticle

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