The α-arrestin SUP-13/ARRD-15 promotes isoform turnover of actin-interacting protein 1 in striated muscle.

Precise arrangement of actin, myosin, and other regulatory components in a sarcomeric pattern is critical for producing contractile forces in striated muscles. Actin-interacting protein 1 (AIP1), also known as WD-repeat protein 1 (WDR1), is one of essential factors that regulate sarcomeric assembly of actin filaments. In the nematode , mutation in , encoding one of the two AIP1 isoforms, causes severe disorganization of sarcomeric actin filaments and near paralysis, but mutation in suppresses the mutant phenotypes to restore nearly normal sarcomeric actin organization and worm motility. Here, we identified that is a nonsense allele of encoding an α-arrestin. The mutation suppressed the phenotypes of null mutant but required that encodes a second AIP1 isoform. was normally expressed highly in embryos and downregulated in mature muscle. However, in the mutant, the AIPL-1 protein was maintained at high levels in adult muscle to compensate for the absence of the UNC-78 protein. The mutation caused accumulation of ubiquitinated AIPL-1 protein, suggesting that a normal function of is to enhance degradation of ubiquitinated AIPL-1, thereby promoting transition of AIP1 isoforms from AIPL-1 to UNC-78 in developing muscle. These results suggest that α-arrestin is a novel factor to promote isoform turnover by enhancing protein degradation.