title: Specific requirement for two ADF/cofilin isoforms in distinct actin-dependent processes in Caenorhabditis elegans.
abstract: Actin depolymerizing factor (ADF)/cofilin is an essential enhancer of actin turnover. Multicellular organisms express multiple ADF/cofilin isoforms in different patterns of tissue distribution. However, the functional significance of different ADF/cofilin isoforms is not understood. The Caenorhabditis elegans unc-60 gene generates two ADF/cofilins, UNC-60A and UNC-60B, by alternative splicing. These two ADF/cofilin proteins have different effects on actin dynamics in vitro, but their functional difference in vivo remains unclear. Here, we demonstrate that the two isoforms are expressed in different tissues and are required for distinct morphogenetic processes. UNC-60A was ubiquitously expressed in most embryonic cells and enriched in adult gonads, intestine and oocytes. In contrast, UNC-60B was specifically expressed in the body wall muscle, vulva and spermatheca. RNA interference of UNC-60A caused embryonic lethality with variable defects in cytokinesis and developmental patterning. In severely affected embryos, a cleavage furrow was formed and progressed but reversed before completion of the cleavage. Also, in some affected embryos, positioning of the blastomeres became abnormal, which resulted in embryonic arrest. In contrast, an unc-60B-null mutant was homozygous viable, underwent normal early embryogenesis and caused disorganization of actin filaments specifically in body wall muscle. These results suggest that the ADF/cofilin isoforms play distinct roles in specific aspects of actin reorganization in vivo.
authors.affiliation: Department of Pathology, Emory University, Whitehead IO5N, Atlanta, Georgia 30322, USA.
authors.forename: Kanako
authors.initials: K
authors.lastname: Ono
authors.forename: Mana
authors.initials: M
authors.lastname: Parast
authors.forename: Christine
authors.initials: C
authors.lastname: Alberico
authors.forename: Guy M
authors.initials: GM
authors.lastname: Benian
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Ono
mesh_terms: D051339:Actin Depolymerizing Factors; D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000483:Alleles; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000502:physiology*; D002455:Cell Division; D051345:Destrin; D018507:Gene Expression Regulation, Developmental; D006720:Homozygote; D008840:Microfilament Proteins / Q000737:chemistry* / Q000502:physiology*; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D008957:Models, Genetic; D009068:Movement; D009154:Mutation; D020033:Protein Isoforms; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D029742:Caenorhabditis elegans Proteins; D051345:Destrin; D008840:Microfilament Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C495209:UNC-60 protein, C elegans