Isoform-specific roles of the Drosophila filamin-type protein Jitterbug (Jbug) during development

ABSTRACTFilamins are highly conserved actin-crosslinking proteins that regulate organization of the actin cytoskeleton. As key components of versatile signaling scaffolding complexes, filamins are implicated in developmental anomalies and cancer. Multiple isoforms of filamins exist, raising the possibility of distinct functions of each isoform during development and in diseases. Here, we provide an initial characterization of jitterbug (jbug), which encodes one of the two filamin-type genes in Drosophila. We generate Jbug antiserum that recognizes all of the spliced forms, which reveals differential expression of different Jbug isoforms during development with a significant maternal contribution of Jbug protein. To reveal the function of Jbug isoforms, we create new genetic tools, including a null allele that deletes all isoforms, hypomorphic alleles that affect only a subset, and UAS lines for expression of the major isoforms. Using these tools, we demonstrate that Jbug is required for viability and that specific isoforms of Jbug are required in the formation of actin-rich protrusions such as thoracic bristles in adults and ventral denticles in the embryo. We also provide evidence for trans-splicing in the jbug locus.