The Exocyst Component Sec3Is Required For Border Cell Migration In Drosophila

Cell migration plays an important role in many physiological and pathological processes, including embryogenesis, immune responses, wound healing, and cancer cell metastasis. Understanding of the mechanisms of cell migration may lead us to develop novel therapeutic strategies for controlling human disease. Border cell migration in the ovary of Drosophila melanogaster has emerged as an excellent model for studying cell migration in vivo. In a screen to uncover novel genes and mechanisms essential for border cell migration, we found that the gene sec3that encodes a component of Drosophila exocyst is required for border cell migration.sec3mutant border cells display strong migration defects. We found that sec3mutant border cell clusters can not display polarized phospho-tyrosine staining and fail to form lamellipodial protrusion. Interestingly, there are strong E-cadherin and Armadillo accumulation around the cell membrane in sec3mutant border cells. Since wild type border cells retain some epithelial characteristics during their migration, the epithelial polarity markers E-cadherin and Armadillo (adherens junction) are normally present in the border cells. Consistently, the strong accumulation of these proteins are also observed beneath the apical cell membrane in the mutant clones in the follicle epithelium. In contrast, we found no defects in the localization pattern of Bazooka (apical junctional marker) and Disc large (lateral junctional marker), in mutant cells of both border cells and follicle cells. We also found that the recycling endosome marker Rab11is also strongly accumulated around the cell membrane of mutant cells, and these Rabll stained vesicles colocalize with the accumulated cytoplasmic E-cad stainings, suggesting Sec3regulates the fusion of recycling vesicles, which contain polarity markers, to the cell membrane.Moreover, we found that sec3interacts with other genes encoding exocyst components during border cell migration, and importantly, we also found that the asymmetry localization of Rab11and Sec5(another component of exocyst) in the front of border cell cluster is mediated by guidance receptors, PVR and EGFR. Taken together, these results suggest that in response to the guidance receptor signaling, Sec3functions to promote polarized transport, targeting and fusion of enssential migration molecules to the membrane of border cells during the guided migration. This research implicates that exocyst and recycling endosomes play important roles in the establishment of polarity during border cell migration, and our study represents the first genetic analysis of sec3in Drosophila.