Title

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

UMMS Affiliation

Department of Cell and Developmental Biology

Date

2-1-2011

Document Type

Article

Medical Subject Headings

Adult; Animals; Cell Nucleus; Cells, Cultured; Gene Knockdown Techniques; HeLa Cells; Humans; Mice; Mice, Inbred C57BL; Muscle Fibers, Skeletal; Muscular Dystrophy, Facioscapulohumeral; Myofibrils; Nuclear Proteins; Sarcomeres

Disciplines

Cell Biology | Developmental Biology | Molecular Biology | Molecular Genetics | Musculoskeletal Diseases | Nervous System Diseases

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. Elsevier B.V. All rights reserved.

Rights and Permissions

Citation: Differentiation. 2011 Feb;81(2):107-18. doi: 10.1016/j.diff.2010.09.185. Link to article on publisher's site

Comments

At the time of publication, Peter Jones was not yet affiliated with the University of Massachusetts Medical School.

Related Resources

Link to Article in PubMed

Keywords

Facioscapulohumeral muscular dystrophy; FRG1; muscle; Z-disc; sarcomere

PubMed ID

20970242