dEHBP1 is localized at the plasma membrane of photoreceptors. (A–C) In an XZ single confocal slice of third-instar eye imaginal disc expressing the actin marker LifeAct EGFP (C), endogenous dEHBP1 (B) colocalizes with the actin cytoskeleton. (B) (D–G) dEHBP1 (E) colocalizes with membrane molecules FasIII (F) and HRP (G) in developing neurons in larval eye imaginal discs. Scale bars: 10 nm. (H) Schematic model of Sca secretion in R8 photorecetors where AP-1γ vesicles bearing Sca travel down actin-rich filopodia. dEHBP1 localizes at the plasma membrane where it regulates a late step in the exocytosis of Sca. When the integrity of the actin cytoskeleton is challenged, as for example upon application of cytochalasin D, transfer of Sca vesicles down the actin-rich tracks is known to be perturbed (Chou and Chien, 2002). However, we propose that actin might also affect other aspects of Notch signaling, such as the endocytosis of Sca, which might also result in defective lateral inhibition during development of R8 photoreceptors (Li et al., 2003). In the absence of dEHBP1, Sca vesicles travel down their path but fail to exocytose, resulting in intracellular accumulation of Sca.