Myopathy mutations in alpha-skeletal-muscle actin cause a range of molecular defects.

Mutations in the gene encoding alpha-skeletal-muscle actin, ACTA1, cause congenital myopathies of various phenotypes that have been studied since their discovery in 1999. Although much is now known about the clinical aspects of myopathies resulting from over 60 different ACTA1 mutations, we have very little evidence for how mutations alter the behavior of the actin protein and thus lead to disease. We used a combination of biochemical and cell biological analysis to classify 19 myopathy mutants and found a range of defects in the actin.

Evidence for sequential utilization of fibronectin, vitronectin, and collagen during fibroblast-mediated collagen contraction.

Contraction plays a major role in wound healing and is inevitably mediated through the mechanical interaction of fibroblast cytoskeleton and integrins with their extracellular matrix ligands. Cell-matrix attachment is critical for such events. In human dermal fibroblasts most such interactions are mediated by the beta1-type integrins.

Enhanced fibroblast contraction of 3D collagen lattices and integrin expression by TGF-beta1 and -beta3: mechanoregulatory growth factors?

Generation of contractile forces as fibroblasts attach and migrate through collagenous substrates is a fundamental behavior, yet its regulation and consequences are obscure. Although the transforming growth factor-betas (TGF-beta) are similarly important in fibrosis and tissue repair, their role in contraction is controversial. Using a quantitative, 3D collagen culture model we have measured the effects of TGF-beta1 and -beta3 on contractile forces generated by human dermal fibroblasts.