title: Guidance receptor promotes the asymmetric distribution of exocyst and recycling endosome during collective cell migration.
abstract: During collective migration, guidance receptors signal downstream to result in a polarized distribution of molecules, including cytoskeletal regulators and guidance receptors themselves, in response to an extracellular gradient of chemotactic factors. However, the underlying mechanism of asymmetry generation in the context of the migration of a group of cells is not well understood. Using border cells in the Drosophila ovary as a model system for collective migration, we found that the receptor tyrosine kinase (RTK) PDGF/VEGF receptor (PVR) is required for a polarized distribution of recycling endosome and exocyst in the leading cells of the border cell cluster. Interestingly, PVR signaled through the small GTPase Rac to positively affect the levels of Rab11-labeled recycling endosomes, probably in an F-actin-dependent manner. Conversely, the exocyst complex component Sec3 was required for the asymmetric localization of RTK activity and F-actin, similar to that previously reported for the function of Rab11. Together, these results suggested a positive-feedback loop in border cells, in which RTKs such as PVR act to induce a higher level of vesicle recycling and tethering activity in the leading cells, which in turn enables RTK activity to be distributed in a more polarized fashion at the front. We also provided evidence that E-cadherin, the major adhesion molecule for border cell migration, is a specific cargo in the Rab11-labeled recycling endosomes and that Sec3 is required for the delivery of the E-cadherin-containing vesicles to the membrane.
authors.affiliation: Model Animal Research Center, and MOE Key Laboratory of Model Animals for Disease Study, Nanjing University, Nanjing, China 210061.
authors.forename: Ping
authors.initials: P
authors.lastname: Wan
authors.forename: Dou
authors.initials: D
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.forename: Dandan
authors.initials: D
authors.lastname: Chu
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.forename: Jiong
authors.initials: J
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D029721:Drosophila Proteins; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor; D020744:rac GTP-Binding Proteins
keywords: Collective cell migration; Drosophila; Exocyst; Guidance receptor; Rab11; Recycling endosome; Sec3