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SPARC Interacts with Actin in Skeletal Muscle in Vitro and in Vivo

Lookup NU author(s): Dr Louise Jorgensen, Professor Hanns Lochmuller

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Abstract

The cytoskeleton is an integral part of skeletal muscle structure, and reorganization of the cytoskeleton occurs during various modes of remodeling. We previously found that the extracellular matrix protein secreted protein acidic and rich in cysteine (SPARC) is up-regulated and expressed intracellularly in developing muscle, during regeneration and in myopathies, which together suggests that SPARC might serve a specific role within muscle cells. Using co-immunoprecipitation combined with mass spectrometry and verified by staining for direct protein-protein interaction, we find that SPARC binds to actin. This interaction is present in regenerating myofibers of patients with Duchenne muscular dystrophy, polymyositis, and compartment syndrome. Analysis of the alpha-, beta-, and gamma-actin isoforms in SPARC knockout myoblasts reveals a changed expression pattern with dominance of gamma-actin. In SPARC knockout mice, we performed an injury study to investigate whether lack of SPARC would compromise the ability to repair muscle. We report that these mice develop normal skeletal muscle with retained ability to regenerate. However, when we subject muscle from SPARC-deficient mice to an in vitro fatigue stimulation protocol, we find a defective force recovery. Therefore, SPARC appears to be an important modulator of the actin cytoskeleton, implicating maintenance of muscular function. This direct interaction with actin suggests a new role of SPARC during tissue remodeling.

Publication metadata

Author(s): Jorgensen LH, Jepsen PL, Boysen A, Dalgaard LB, Hvid LG, Ortenblad N, Ravn D, Sellathurai J, Moller-Jensen J, Lochmuller H, Schroder HD

Publication type: Article

Publication status: Published

Journal: American Journal of Pathology

Year: 2017

Volume: 187

Issue: 2

Pages: 457-474

Print publication date: 01/02/2017

Online publication date: 29/11/2016

Acceptance date: 18/10/2016

ISSN (print): 0002-9440

ISSN (electronic): 1525-2191

Publisher: Elsevier

URL: http://dx.doi.org/10.1016/j.ajpath.2016.10.013

DOI: 10.1016/j.ajpath.2016.10.013

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