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Rab11 regulates cell-cell communication during collective cell movements.
- Source :
-
Nature cell biology [Nat Cell Biol] 2013 Mar; Vol. 15 (3), pp. 317-24. Date of Electronic Publication: 2013 Feb 03. - Publication Year :
- 2013
-
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.
- Subjects :
- Actin Cytoskeleton
Animals
Drosophila Proteins genetics
Drosophila melanogaster metabolism
Flow Cytometry
Fluorescence Resonance Energy Transfer
Immunoprecipitation
Membrane Proteins genetics
RNA, Small Interfering genetics
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
rab GTP-Binding Proteins genetics
rab5 GTP-Binding Proteins genetics
rac GTP-Binding Proteins genetics
Cell Communication
Cell Movement physiology
Drosophila Proteins metabolism
Drosophila melanogaster genetics
Membrane Proteins metabolism
rab GTP-Binding Proteins metabolism
rab5 GTP-Binding Proteins metabolism
rac GTP-Binding Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4679
- Volume :
- 15
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Nature cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 23376974
- Full Text :
- https://doi.org/10.1038/ncb2681