Two distinct integrin-mediated mechanisms contribute to apical lumen formation in epithelial cells

PLoS One. 2011 May 6;6(5):e19453. doi: 10.1371/journal.pone.0019453.


Background: Formation of apical compartments underlies the morphogenesis of most epithelial organs during development. The extracellular matrix (ECM), particularly the basement membrane (BM), plays an important role in orienting the apico-basal polarity and thereby the positioning of apical lumens. Integrins have been recognized as essential mediators of matrix-derived polarity signals. The importance of β1-integrins in epithelial polarization is well established but the significance of the accompanying α-subunits have not been analyzed in detail.

Principal findings: Here we demonstrate that two distinct integrin-dependent pathways regulate formation of apical lumens to ensure robust apical membrane biogenesis under different microenvironmental conditions; 1) α2β1- and α6β4-integrins were required to establish a basal cue that depends on Rac1-activity and guides apico-basal cell polarization. 2) α3β1-integrins were implicated in positioning of mitotic spindles in cysts, a process that is essential for Cdc42-driven epithelial hollowing.

Significance: Identification of the separate processes driven by particular integrin receptors clarifies the functional hierarchies between the different integrins co-expressed in epithelial cells and provides valuable insight into the complexity of cell-ECM interactions thereby guiding future studies addressing the molecular basis of epithelial morphogenesis during development and disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / genetics
  • Cell Adhesion / physiology
  • Cell Line
  • Cell Polarity / genetics
  • Cell Polarity / physiology
  • Dogs
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism*
  • Fluorescent Antibody Technique
  • Immunoblotting
  • Integrin alpha2beta1 / genetics
  • Integrin alpha2beta1 / metabolism*
  • Integrin alpha3beta1 / genetics
  • Integrin alpha3beta1 / metabolism
  • Integrin alpha6beta4 / genetics
  • Integrin alpha6beta4 / metabolism*
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • RNA, Small Interfering


  • Integrin alpha2beta1
  • Integrin alpha3beta1
  • Integrin alpha6beta4
  • RNA, Small Interfering