title: Rab11 regulates cell-cell communication during collective cell movements.
abstract: Collective cell movements contribute to development and metastasis. The small GTPase Rac is a key regulator of actin dynamics and cell migration but the mechanisms that restrict Rac activation and localization in a group of collectively migrating cells are unknown. Here, we demonstrate that the small GTPases Rab5 and Rab11 regulate Rac activity and polarization during collective cell migration. We use photoactivatable forms of Rac to demonstrate that Rab11 acts on the entire group to ensure that Rac activity is properly restricted to the leading cell through regulation of cell-cell communication. In addition, we show that Rab11 binds to the actin cytoskeleton regulator Moesin and regulates its activation in vivo during migration. Accordingly, reducing the level of Moesin activity also affects cell-cell communication, whereas expressing active Moesin rescues loss of Rab11 function. Our model suggests that Rab11 controls the sensing of the relative levels of Rac activity in a group of cells, leading to the organization of individual cells in a coherent multicellular motile structure.
authors: Institute for Research in Immunology and Cancer (IRIC) and Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, Quebec, H3C 3J7, Canada.
authors: Damien
authors: D
authors: Ramel
authors: Xiaobo
authors: X
authors: Wang
authors: Carl
authors: C
authors: Laflamme
authors: Denise J
authors: DJ
authors: Montell
authors: Gregory
authors: G
authors: Emery
mesh_terms: D008841:Actin Cytoskeleton; D000818:Animals; D002450:Cell Communication; D002465:Cell Movement / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D031541:Fluorescence Resonance Energy Transfer; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins; D020744:rac GTP-Binding Proteins; C099886:moesin, Drosophila; C559123:Rab11 protein, Drosophila; D000099193:rab11 GTP-Binding Proteins
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