Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) is a dynamic nuclear and sarcomeric protein

Meredith L. Hanel, Chia Yun Jessica Sun, Takako I. Jones, Steven W. Long, Simona Zanotti, Derek Milner, Peter L. Jones

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) is a candidate gene for mediating FSHD pathophysiology, however, very little is known about the endogenous FRG1 protein. This study uses immunocytochemistry (ICC) and histology to provide insight into FRG1's role in vertebrate muscle development and address its potential involvement in FSHD pathophysiology. In cell culture, primary myoblast/myotube cultures, and mouse and human muscle sections, FRG1 showed distinct nuclear and cytoplasmic localizations and nuclear shuttling assays indicated the subcellular pools of FRG1 are linked. During myoblast differentiation, FRG1's subcellular distribution changed dramatically with FRG1 eventually associating with the matured Z-discs. This Z-disc localization was confirmed using isolated mouse myofibers and found to be maintained in adult human skeletal muscle biopsies. Thus, FRG1 is not likely involved in the initial assembly and alignment of the Z-disc but may be involved in sarcomere maintenance or signaling. Further analysis of human tissue showed FRG1 is strongly expressed in arteries, veins, and capillaries, the other prominently affected tissue in FSHD. Overall, we show that in mammalian cells, FRG1 is a dynamic nuclear and cytoplasmic protein, however in muscle, FRG1 is also a developmentally regulated sarcomeric protein suggesting FRG1 may perform a muscle-specific function. Thus, FRG1 is the only FSHD candidate protein linked to the muscle contractile machinery and may address why the musculature and vasculature are specifically susceptible in FSHD.

Original languageEnglish
Pages (from-to)107-118
Number of pages12
JournalDifferentiation
Volume81
Issue number2
DOIs
Publication statusPublished - Feb 2011

Fingerprint

Facioscapulohumeral Muscular Dystrophy
Nuclear Proteins
Genes
Muscles
Myoblasts
Sarcomeres
Proteins
Muscle Development
Skeletal Muscle Fibers
Vertebrates
Veins

Keywords

  • Facioscapulohumeral muscular dystrophy
  • FRG1
  • Muscle
  • Sarcomere
  • Z-disc

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology
  • Cancer Research

Cite this

Hanel, M. L., Sun, C. Y. J., Jones, T. I., Long, S. W., Zanotti, S., Milner, D., & Jones, P. L. (2011). Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) is a dynamic nuclear and sarcomeric protein. Differentiation, 81(2), 107-118. https://doi.org/10.1016/j.diff.2010.09.185

Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) is a dynamic nuclear and sarcomeric protein. / Hanel, Meredith L.; Sun, Chia Yun Jessica; Jones, Takako I.; Long, Steven W.; Zanotti, Simona; Milner, Derek; Jones, Peter L.

In: Differentiation, Vol. 81, No. 2, 02.2011, p. 107-118.

Research output: Contribution to journalArticle

Hanel, ML, Sun, CYJ, Jones, TI, Long, SW, Zanotti, S, Milner, D & Jones, PL 2011, 'Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) is a dynamic nuclear and sarcomeric protein', Differentiation, vol. 81, no. 2, pp. 107-118. https://doi.org/10.1016/j.diff.2010.09.185
Hanel, Meredith L. ; Sun, Chia Yun Jessica ; Jones, Takako I. ; Long, Steven W. ; Zanotti, Simona ; Milner, Derek ; Jones, Peter L. / Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) is a dynamic nuclear and sarcomeric protein. In: Differentiation. 2011 ; Vol. 81, No. 2. pp. 107-118.
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