Bifocal is a downstream target of the Ste20-like serine/threonine kinase misshapen in regulating photoreceptor growth cone targeting in Drosophila

Misshapen (Msn) has been proposed to shut down Drosophila photoreceptor (R cell) growth cone motility in response to targeting signals linked by the SH2/SH3 adaptor protein Dock. Here, we show that Bifocal (Bif), a putative cytoskeletal regulator, is a component of the Msn pathway for regulating R cell growth cone targeting. bif displays strong genetic interaction with msn. Phenotypic analysis indicates a specific role for Bif to terminate R1-R6 growth cones. Biochemical studies show that Msn associates directly with Bif and phosphorylates Bif in vitro. Cell culture studies demonstrate that Msn interacts with Bif to regulate F-actin structure and filopodium formation. We propose that Bif functions downstream of Msn to reorganize actin cytoskeleton in decelerating R cell growth cone motility at the target region.