Shoichiro Ono

The Shoichiro's lab primary research interest is the mechanisms that regulate dynamic rearrangement of the actin cytoskeleton during various cellular events including development, cell movement, cytokinesis, and human diseases. We have been studying this problem using the nematode Caenorhabditis elegans as a model system. C. elegans has been used to study many aspects of development, because of its relative simplicity in the body patterning, and application of genetics, molecular biology, biochemistry, and cell biology. We are especially interested in the functions of the actin depolymerizing factor (ADF)/cofilin family of actin-binding proteins, which are required for enhancement of actin filament dynamics. We found that two ADF/cofilin proteins that are generated from the unc-60 gene have different actin-regulating activities. Mutation and expression analyses demonstrated that one of the two ADF/cofilin isoforms (UNC-60B) was specifically required for organized assembly of actin filaments in muscle. ADF/cofilin promotes depolymerization and severing of actin filaments, but tropomyosin inhibits this effect by stabilizing filaments. The other ADF/cofilin isoform (UNC-60A) is highly expressed in early embryos and regulates cytokinesis and embryonic patterning. In addition, we found that actin-interacting protein 1 (AIP1) is a new regulator of muscle actin filaments. AIP1 (UNC-78) specifically interacts with ADF/cofilin-bound actin filaments and enhances filament depolymerization. We also found that the gene product of sup-12 (an RBM24 homolog) regulates alternative splicing of the unc-60 gene and is required for generation of the unc-60B mRNA. We are currently studying functions of these proteins and other regulators of actin dynamics in several developmental aspects in C. elegans.