Mutations in the
unc-78 gene result in slow-moving worms that have large aggregates of thin filaments at the ends of spindle-shaped body wall muscle cells. Therefore, the
unc-78 gene has been implicated in proper organization of actin filaments into myofibrils. In addition,
unc-78 mutations affect total integrity of the myofilament lattice (Welborne et al., 1997 Int. Worm Meeting). We characterized phenotypes of homozygous
unc-78 mutants. By observing their motility,
unc-78(
su152) was very slow, whereas
unc-78(
e1217) and
unc-78(
su135) were only slightly slower than wild-type and
unc-78(
e1221) and
unc-78(
su187) moved comparable to wild-type. Phalloidin-staining of whole worms revealed that large aggregates of actin filaments were formed in almost all body wall muscle cells of
unc-78(
e1217). In contrast,
unc-78(
e1221) had well-organized actin filaments as well as relatively smaller actin aggregates only in a subset of body wall muscle cells. In addition, we noted that actin filaments in L1 to L3 larvae appeared normal even in severe
unc-78 mutants, suggesting that
unc-78 is involved in growth and/or maintenance of the myofibrils. We identified sequence alterations in a gene, C04F6.4, from four
unc-78 alleles. C04F6.4 has been predicted to encode a protein of 65 kDa that contains 9 WD-repeats. All four alleles are missense mutations at conserved residues within WD-repeats. The mutation sites are located in the forth repeat for
unc-78(
su135), the fifth repeat for
unc-78(
e1217) and the eighth repeat for
unc-78(
e1221) and
unc-78(
su187) (same mutations). The predicted C04F6.4 protein is homologous to actin-interacting protein 1 (AIP1). AIP1 has been identified in yeast, slime molds and vertebrates and shown to be involved in dynamic reorganization of actin cytoskeleton. Moreover, AIP1 has been demonstrated to interact with ADF/cofilin and potentiate its actin-depolymerizing activity. Likewise, preliminary results showed that UNC-60B, a worm ADF/cofilin isoform, was mislocalized to the actin aggregates in
unc-78 mutants. Thus, UNC-78 is a likely regulator of actin filament dynamics in body wall muscle.