Kevin Blacketor

I have been working on the molecular nature of the disease myosin storage myopathy.  Myosin storage myopathy is a congenital myopathy characterized by subsarcolemmal hyaline bodies in type 1 skeletal muscle that are composed, at least in part, of ß-myosin (MyHC).  Recent reports have linked the disease to two heterozygous missense mutations; R1845W in Swedish and Belgian families, and H1901L in a large Saudi kindred. It is interesting that although ß-MyHC is expressed in both the heart (at high levels) and skeletal muscle, the skeletal myopathy occurs in the absence of any apparent cardiomyopathy.

Both mutations occur in the c-terminal LMM region of the MyHC rod.  The MyHC rod is a coiled-coil, and both mutations are located in the outer “f” position which is thought to mediate the interaction between coiled-coils during thick filament formation.  Therefore, it has been hypothesized in the literature that myosin storage myopathy results from a defect in thick filament assembly.  I am currently testing how these mutations alter assembly in vitro and in vivo, as well as how muscle function is affected and how interactions between LMM and sarcomeric proteins may be affected.