Role of synemin, an intermediate filament protein, in adult skeletal muscle (1102.25)

Abstract

Intermediate filament (IF) related diseases are linked to defects in proteins that are associated with the contractile apparatus of skeletal and cardiac muscle, and with costameres. Synemin is a large IF protein that associates with dystrobrevin, vinculin, and talin at costameres at the sarcolemma of striated muscle, as well as with α‐actinin and desmin at Z disks. Synemin can be expressed in either 210 kDa α‐ or 180 kDa β‐ alternatively spliced forms. We generated mice null for synemin by homologous recombination to study synemin’s function in skeletal muscle. Skeletal muscle in the knock out (syn KO) mouse does not make synemin mRNA or protein. Preliminary characterization of the syn KO mouse suggests that it has a mild skeletal muscle phenotype. The organization of costameres appears to be normal, but the fibers appear smaller than controls. Treadmill running uphill test results was not significantly affected when compared to controls. More notably, we have observed differences in the biomechanical properties of the sarcolemma. Stabilization time of blebs generated by applying fixed suction pressure through a pipette to the surface membrane of single Extensor digitorum longus fibers, were slower in the syn KO than in controls but faster than in desmin KO and mdx fibers, which lack dystrophin. Furthermore, the pressure at which the blebs separated from underlying contractile structures were lower than in controls. These results suggest that the viscoelastic properties of the sarcolemma‐costamere‐myofibril complex are significantly influenced by synemin, but less than by desmin and dystrophin.Grant Funding Source: Supported by APS Postdoctoral Fellowship Physiological Genomics and CONACyT to KGP. By NIH to RJB