A Genetic Screen Identifies Myo-V as a Component of Abl Signaling Pathways. Sierra K. Mosticone-Wangensteen, Traci L. Stevens. Biology, Randolph-Macon College, Ashland, VA.

   Abl is a nonreceptor tyrosine kinase that regulates the cytoskeleton and cell migration. Mutations in abl alter actin structure and cell migration, and unregulated cell migration is a hallmark of cancer. Chronic myelogenous leukemia, which is caused by the expression of an activated form of Abl (Bcr-Abl) that results from a chromosomal translocation, is linked to the inappropriate migration of the white blood cells. In Drosophila, expression of Bcr-Abl in the epithelium causes defects in embryonic processes that require regulated cell migration such as head involution and dorsal closure. Although we know that Abl regulates cell migration, we do not know all the elements of the pathway by which it regulates the cytoskeleton. Our laboratory is doing a deficiency screen to identify regions that contain genes that interact with the activated form of Abl, Bcr-Abl, and therefore are likely to encode proteins that act in the Abl pathway. Here, our goal was to narrow down a region defined by two large overlapping deficiencies of the second chromosome that suppress the effects of Bcr-Abl expression to identify the gene(s) within this region that genetically interacts with Bcr-Abl. As a first approach, we tested seven smaller deficiencies that overlap with the deficiencies that suppress. Most of these smaller deficiencies did not interact, but surprisingly, we found that two of these smaller deficiencies enhanced the phenotypes associated with Bcr-Abl expression, suggesting that more than one gene in this region may genetically interact with expression of Bcr-Abl. In addition, we tested mutant alleles of fifteen individual genes in this region of the genome, and we found that two different mutant alleles of didum, which encodes Myosin-V (Myo-V), an unconventional actin-based motor, suppressed the phenotypes associated with Bcr-Abl expression. These results provide in vivo evidence that Myo-V plays a role in Abl signaling pathways, and future experiments will be done to examine the function of Myo-V in the pathways that regulate cell migration.