Regulation of epithelial morphogenesis in Drosophila by the Emp scavenger receptor

Sammanfattning: The respiratory system of Drosophila melanogaster, the trachea, is widely used as a model system to study the development of branched tubular organs. Airway maturation in Drosophila entails a series of sequential events: first, a massive apical secretion of luminal proteins initiates diametric tube expansion, second an endocytic wave removes luminal proteins and finally liquid clearance and gas filling converts the nascent epithelial tubes to a functional respiratory organ. Several studies have highlighted the importance of luminal protein clearance by endocytosis, however cargo specific receptors mediating protein uptake remain unknown. We characterized the Drosophila homologue of CD36 (scavenger receptor protein class B), Emp (epithelial membrane protein). Embryos lacking emp display over elongated tracheal tubes and fail to clear a subset of luminal chitin binding proteins before hatching. Emp shows a dynamic localization between endosomes and apical/sub-apical regions of epithelial cells during tube maturation. The apical punctate localization of Emp depends on intact F-actin filaments. In turn, Emp organizes the apical cytoskeleton through its binding to βH-Spectrin. In emp mutants the apical membrane levels of Crb and DE-cad are perturbed and phosphorylation of Src42A (pSrc) at the adherens epithelial junctions are increased. We show that Emp is a downstream target of Yki and physically interacts with Diap1 (Death-associated inhibitor of apoptosis 1) thereby controlling the activation of DrICE (Death related ICE-like caspase). A Y2H screen and co-immunoprecipitation, revealed that Emp interacts with the GTPase activating protein, CG32506. We speculate that CG32506 acts as an antagonist of Emp in regulating Src42A phosphorylation and the downstream targets of the Yki pathway Diap1 and DrICE. Overall, we show that Emp is a selective scavenger receptor for endocytosis, regulating apical cytoskeletal integrity. We defined intracellular components of Emp-mediated endocytosis and cargo recycling route including effectors of apoptosis and components of the Hippo signaling pathway.