title: Insights into the effects of disease-causing mutations in human actins.
abstract: Mutations in all six actins in humans have now been shown to cause diseases. However, a number of factors have made it difficult to gain insight into how the changes in actin functions brought about by these pathogenic mutations result in the disease phenotype. These include the presence of multiple actins in the same cell, limited accessibility to pure mutant material, and complexities associated with the structures and their component cells that manifest the diseases. To try to circumvent these difficulties, investigators have turned to the use of model systems. This review describes these various approaches, the initial results obtained using them, and the insight they have provided into allosteric mechanisms that govern actin function. Although results so far have not explained a particular disease phenotype at the molecular level, they have provided valuable insight into actin function at the mechanistic level which can be utilized in the future to delineate the molecular bases of these different actinopathies.
authors.affiliation: Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Rubenstein
authors.forename: Kuo-Kuang
authors.initials: KK
authors.lastname: Wen
mesh_terms: D000199:Actins / Q000737:chemistry / Q000235:genetics*; D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D004194:Disease / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics
chemical_list: D000199:Actins; D020033:Protein Isoforms
keywords: actin; allostery; disease; isoforms; mutation