Syncoilin upregulation in muscle of patients with neuromuscular disease

Abstract

Syncoilin may have a role in linking the desmin-associated intermediate filament network of the muscle fiber with the dystrophin-associated protein complex (DAPC). We have evaluated syncoilin in a range of neuromuscular disorders including Duchenne and Becker muscular dystrophy, central core disease, congenital muscular dystrophies, and neurogenic disorders. Our results show that syncoilin immunolabeling is not only altered in muscle fibers with alterations in the DAPC but also in response to a variety of genetic defects, including those associated with proteins of the extracellular matrix and the intracellular Ca2+-release channel (ryanodine receptor). The pattern of syncoilin immunolabeling in these diseases appeared to reflect a rearrangement of the intermediate filament-associated cytoskeleton that characterizes both muscle fiber development and conditions in which the cytoskeletal organization of the muscle fiber is significantly affected. These observations raise the possibility that mutations in the gene encoding for syncoilin may underlie some forms of muscle disease.

Interaction of α-Catulin with Dystrobrevin Contributes to Integrity of Dystrophin Complex in Muscle

“…These proteins include utrophin, ␥-actin, and syncoilin (9,33,34,42). Such compensatory increases have been postulated to fortify the weakened sarcolemma through recruitment of parallel mechanical linkages.…”

“…Furthermore, the expression of these cytoskeletal proteins is increased when the DAPC is compromised. This compensatory increase is thought to play a role in protecting the weakened sarcolemma (9,33,34). Therefore, we compared the expression levels of ␣-catulin in gastrocnemius muscles from 4-week-old wild-type mice and mdx mice, which lack functional dystrophin.…”

Syncoilin is required for generating maximum isometric stress in skeletal muscle but dispensable for muscle cytoarchitecture

“…Furthermore, its upregulation in various neuromuscular diseases (8,18) has suggested that syncoilin may be involved in muscular myopathies. We studied the in vivo role of syncoilin by the generation and detailed analysis of cardiac and skeletal muscle from syncoilin Ϫ/Ϫ mice up to 2 yr of age using histological, TEM, biochemical, molecular, biophysical, and physiological tools.…”

“…Syncoilin transcript levels were unchanged, implying that the reduction in syncoilin protein in the absence of desmin is due to posttranscriptional regulation by either decreased protein translation or protein degradation. The upregulation of syncoilin in dystrophic muscle in various forms of human neuromuscular disease (8,18), as well as in both ␣-dystrobrevin knockout (22) and dystrophin-deficient mdx mice (26,34), further raises the possibility that syncoilin may play a role in human skeletal muscle and cardiac diseases. However, its function remains elusive.…”

Syncoilin modulates peripherin filament networks and is necessary for large-calibre motor neurons

“…Syncoilin has never been observed under normal conditions to form filament structures either alone or with other IF proteins, but thick syncoilin filament-like structures are known to form in some myopathies where syncoilin upregulation occurs (Brown et al, 2005).…”