The Cappuccino interactome reveals an intracellular role for Semaphorin-2a in Drosophila oogenesis

The spatiotemporal regulation of an actin mesh during Drosophila oogenesis is essential for proper localization of cell polarity determinants that establish the future patterning of the embryo. Here, we reveal an unexpected role for Semaphorin-2a (Sema2a) in actin mesh regulation and oogenesis. Sema2a classically functions as a secreted guidance cue that binds its cognate Plexin-B (PlexB) receptor to establish neural circuits. In contrast, we find that Sema2a is expressed inside the germarium, germline, and follicle cells of the developing ovary. Sema2a mutants possess small ovaries that fail to develop past mid-oogenesis. We demonstrate that Sema2a interacts with Cappuccino (Capu), a key actin nucleator crucial for building the actin mesh in Drosophila oocytes. Sema2a inhibits the actin assembly activity of Capu in vitro. Furthermore, genetic interaction between Sema2a and Capu influences mesh density and disrupts oskar mRNA localization. PlexB mutants, however, exhibit wild-type size ovaries with oskar mRNA localization distinct from Sema2a mutants, confirming the non-canonical role of Sema2a in oogenesis.