The Caenorhabditis elegans unc-78 gene encodes a homologue of actin-interacting protein 1 required for organized assembly of muscle actin filaments.
Assembly and maintenance of myofibrils require dynamic regulation of the actin cytoskeleton. In Caenorhabditis elegans, UNC-60B, a muscle-specific actin depolymerizing factor (ADF)/cofilin isoform, is required for proper actin filament assembly in body wall muscle (Ono, S., D.L. Baillie, and G.M. Benian. 1999. J. Cell Biol. 145:491--502). Here, I show that UNC-78 is a homologue of actin-interacting protein 1 (AIP1) and functions as a novel regulator of actin organization in myofibrils. In unc-78 mutants, the striated organization of actin filaments is disrupted, and large actin aggregates are formed in the body wall muscle cells, resulting in defects in their motility. Point mutations in unc-78 alleles change conserved residues within different WD repeats of the UNC-78 protein and cause less severe phenotypes than a deletion allele, suggesting that these mutations partially impair the function of UNC-78. UNC-60B is normally localized in the diffuse cytoplasm and to the myofibrils in wild type but mislocalized to the actin aggregates in unc-78 mutants. Similar Unc-78 phenotypes are observed in both embryonic and adult muscles. Thus, AIP1 is an important regulator of actin filament organization and localization of ADF/cofilin during development of myofibrils.
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Department of Pathology, Emory University, Atlanta, Georgia 30322, USA. sono@emory.edu
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009068:Movement; D009154:Mutation; D009210:Myofibrils / Q000737:chemistry / Q000378:metabolism*; D010802:Phylogeny; D016415:Sequence Alignment
D000199:Actins; D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D008840:Microfilament Proteins; C495209:UNC-60 protein, C elegans; C423987:unc-78 protein, C elegans