RhoL controls invasion and Rap1 localization during immune cell transmigration in Drosophila

Human immune cells penetrate an endothelial barrier during their beneficial pursuit of infection and their destructive infiltration in autoimmune diseases. This transmigration requires Rap1 GTPase to activate Integrin affinity1. We define a new model system for this process by demonstrating with live imaging and genetics that during embryonic development, Drosophila melanogaster immune cells penetrate an epithelial, DE-Cadherin-based tissue barrier. A mutant in RhoL, a GTPase homolog that is specifically expressed in hemocytes, blocks this invasive step but not other aspects of guided migration. RhoL mediates Integrin adhesion caused by Drosophila Rap1 over-expression and moves Rap1 away from a cytoplasmic concentration to the leading edge during invasive migration. These findings indicate that a programmed migratory step during Drosophila development bears striking molecular similarities to vertebrate immune cell transmigration during inflammation and identify RhoL as a new regulator of invasion, adhesion and Rap1 localization. Our work establishes the utility of Drosophila for identifying novel components of immune cell transmigration and for understanding the in vivo interplay of immune cells with the barriers they penetrate.