The spectrin superfamily (spectrin, alpha-actinin, utrophin and dystrophin) has in common a triple helical repeating unit of ~106 amino acid residues. In spectrin, alpha and beta chains contain multiple copies of this repeat. beta-spectrin chains contain the majority of binding activities in spectrin and are essential for animal life. Canonical beta-spectrins have 17 repeats; beta-heavy spectri...

Genetically encoded filamentous actin probes, Lifeact, Utrophin and F-tractin, are used as tools to label the actin cytoskeleton. Recent evidence in several different cell types indicates that these probes can cause changes in filamentous actin dynamics, altering cell morphology and function. Although these probes are commonly used to visualise actin dynamics in neurons, their effects on axonal...

In humans, cytoskeletal dystrophin and muscle LIM protein (MLP) gene mutations can cause dilated cardiomyopathy, yet these mutations may have different effects in mice, owing to increased accumulation of other, compensatory cytoskeletal proteins. Consequently, we characterized left-ventricular (LV) morphology and function in vivo using high-resolution cine-magnetic resonance imaging (MRI) in 2-...

Fluorescent derivatives of actin and actin-binding domains are powerful tools for studying actin filament architecture and dynamics in live cells. Growing evidence, however, indicates that these probes are biased, and their cellular distribution does not accurately reflect that of the cytoskeleton. To understand the strengths and weaknesses of commonly used live-cell probes--fluorescent protein...

Utrophin, like its homologue dystrophin, forms a link between the actin cytoskeleton and the extracellular matrix. We have used a new method of image analysis to reconstruct actin filaments decorated with the actin-binding domain of utrophin, which contains two calponin homology domains. We find two different modes of binding, with either one or two calponin-homology (CH) domains bound per acti...

The dystroglycans (alpha-DG and beta-DG), which play important roles in the formation of basement membranes, have been well studied in skeletal muscle and nerve, but their expression and localization in intestinal epithelial cells has not been previously investigated. Here, we demonstrated that the DG complex, composed of alpha-DG, beta-DG, and utrophin, is specifically expressed in the basolat...

SMT C1100 is a small molecule utrophin modulator in development to treat Duchenne muscular dystrophy. This study evaluated the safety, tolerability, and pharmacokinetics of SMT C1100 in healthy volunteers. This double-blind, placebo-controlled Phase 1 study comprised: Part 1, an escalating, single-dose with/without fasting involving 50 mg/kg, 100 mg/kg, 200 mg/kg, and 400 mg/kg doses; and Part ...