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

Louise H Jørgensen, Pia Lørup Jepsen, Anders Boysen, Line Barner Dalgaard, Lars G Hvid, Niels Ørtenblad, Dea Ravn, Jeeva Sellathurai, Jakob Møller-Jensen, Hanns Lochmüller, Henrik D Schrøder

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstrakt

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 α-, β-, and γ-actin isoforms in SPARC knockout myoblasts reveals a changed expression pattern with dominance of γ-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.

OriginalsprogEngelsk
TidsskriftThe American Journal of Pathology
Vol/bind187
Udgave nummer2
Sider (fra-til)457–474
ISSN0002-9440
DOI
StatusUdgivet - 1. feb. 2017

Fingeraftryk Dyk ned i forskningsemnerne om 'SPARC Interacts with Actin in Skeletal Muscle in Vitro and in Vivo'. Sammen danner de et unikt fingeraftryk.

Citationsformater