The attachment disorders of muscle: failure to carb-load

Abstract

Dystroglycan is a prominent cell surface protein that mediates attachment to the extracellular matrix. Although broadly expressed, glycosylated dystroglycan is critically important for muscle cell adherence to its surrounding matrix. A subgroup of muscular dystrophies, which often manifest in infancy, is associated with reduced glycosylation of dystroglycan. In this issue of the JCI, Beedle et al. used conditional gene targeting of Fktn, the gene responsible for Fukuyama congenital muscular dystrophy, to investigate a developmental requirement for glycosylation of dystroglycan.

Figure 1. Shown is a schematic of dystroglycan and its position within the muscle cell membrane.

Dystroglycan is composed of α and β subunits (αDG and βDG). βDG interacts directly with dystrophin, the protein product of the Duchenne muscular dystrophy locus. The sarcoglycan transmembrane complex stabilizes the interaction between αDG and βDG. Glycosylation of αDG is critical for mediating attachment to matrix components including laminin. Mutations in at least seven different genes are associated with reduced αDG glycosylation (listed in the red box), and protein products of these genes encode glycosylases resident to the secretory system. Decreased αDG glycosylation reduces attachment between the membrane and surrounding matrix. Beedle et al. (7) now report three different deletion strategies for FKTN, and show that FKTN loss is associated with dysregulated glycosylation of αDG and muscular dystrophy.