NIH R01 · 2024
C2 domain therapeutics for muscular dystrophy
Mutations in the dysferlin gene (DYSF) cause Limb Girdle Muscular Dystrophy Type 2B (LGMD 2B) and Miyoshi Myopathy (MMD1) and affect ~1:100,000 individuals worldwide. Dysferlin is comprised of ferlin and dysferlin domains flanked by C2 domains and it accumulates in t-tubule membranes (TTs) at triad junctions (TJs). Our labs have been collaborating to learn how DYSF fulfills its two best understood functions in muscle, repair of the sarcolemmal membrane and stabilization of the Ca2+ transient. We recently showed that DYSF’s most N-terminal C2 domain, C2A, plays unique roles in both (Muriel et al., J Physiol. 2022): like WT DYSF, DYSF missing the C2A domain accumulates in TTs at TJs but it…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.