Format

Send to

Choose Destination
Nat Cell Biol. 2013 Mar;15(3):317-24. doi: 10.1038/ncb2681. Epub 2013 Feb 3.

Rab11 regulates cell-cell communication during collective cell movements.

Author information

1
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.

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.

PMID:
23376974
PMCID:
PMC4006229
DOI:
10.1038/ncb2681
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center