Rab11 regulates cell-cell communication during collective cell movements.

TitleRab11 regulates cell-cell communication during collective cell movements.
Publication TypeJournal Article
Year of Publication2013
AuthorsRamel D, Wang X, Laflamme C, Montell DJ, Emery G
JournalNat Cell Biol
Date Published2013 Mar
KeywordsActin Cytoskeleton, Animals, Cell Communication, Cell Movement, Drosophila melanogaster, Drosophila Proteins, Flow Cytometry, Fluorescence Resonance Energy Transfer, Immunoprecipitation, Membrane Proteins, rab GTP-Binding Proteins, rab5 GTP-Binding Proteins, rac GTP-Binding Proteins, RNA, Small Interfering, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

<p>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.</p>

Alternate JournalNat Cell Biol
PubMed ID23376974
PubMed Central IDPMC4006229
Grant ListR01 GM073164 / GM / NIGMS NIH HHS / United States
MOP-114899 / / Canadian Institutes of Health Research / Canada
R01 GM046425 / GM / NIGMS NIH HHS / United States
R01GM46425 / GM / NIGMS NIH HHS / United States
R01GM73164 / GM / NIGMS NIH HHS / United States