Rab11 regulates cell-cell communication during collective cell movements

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton
  • Animals
  • Cell Communication*
  • Cell Movement / physiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Flow Cytometry
  • Fluorescence Resonance Energy Transfer
  • Immunoprecipitation
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • RNA, Small Interfering / genetics
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*
  • rab5 GTP-Binding Proteins / genetics
  • rab5 GTP-Binding Proteins / metabolism*
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism*

Substances

  • Drosophila Proteins
  • Membrane Proteins
  • RNA, Small Interfering
  • moesin, Drosophila
  • Rab11 protein, Drosophila
  • rab GTP-Binding Proteins
  • rab5 GTP-Binding Proteins
  • rac GTP-Binding Proteins