title: Spatial restriction of receptor tyrosine kinase activity through a polarized endocytic cycle controls border cell migration.
abstract: Border cell migration is a stereotyped migration occurring during the development of the Drosophila egg chamber. During this process, a cluster composed of six to eight follicle cells migrates between nurse cells toward the oocyte. Receptor tyrosine kinases (RTKs) are enriched at the leading edge of the follicle cells and establish the directionality of their migration. Endocytosis has been shown to play a role in the maintenance of this polarization; however, the mechanisms involved are largely unknown. In this study, we show that border cell migration requires the function of the small GTPases Rab5 and Rab11 that regulate trafficking through the early and the recycling endosome, respectively. Expression of a dominant negative form of rab11 induces a loss of the polarization of RTK activity, which correlates with a severe migration phenotype. In addition, we demonstrate that the exocyst component Sec15 is distributed in structures that are polarized during the migration process in a Rab11-dependent manner and that the down-regulation of different subunits of the exocyst also affects migration. Together, our data demonstrate a fundamental role for a plasma membrane-endosome trafficking cycle in the maintenance of active RTK at the leading edge of border cells during their migration.
authors.affiliation: Institute for Research in Immunology and Cancer and Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, Quebec, Canada H3C 3J7.
authors.forename: Gloria
authors.initials: G
authors.lastname: Assaker
authors.forename: Damien
authors.initials: D
authors.lastname: Ramel
authors.forename: Stefanie K
authors.initials: SK
authors.lastname: Wculek
authors.forename: Marcos
authors.initials: M
authors.lastname: González-Gaitán
authors.forename: Gregory
authors.initials: G
authors.lastname: Emery
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D034622:RNA Interference; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D018010:Receptors, Invertebrate Peptide / Q000378:metabolism; D013997:Time Factors; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020695:rab4 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins
chemical_list: D029721:Drosophila Proteins; D066246:ErbB Receptors; D008164:Luminescent Proteins; D020794:Receptor Protein-Tyrosine Kinases; D018010:Receptors, Invertebrate Peptide; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins; D020695:rab4 GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C505147:Sec15 protein, Drosophila; C066532:Egfr protein, Drosophila; C438368:Pvr protein, Drosophila