Spatial regulation of Dia and Myosin-II by RhoGEF2 controls initiation of E-cadherin endocytosis during epithelial morphogenesis

Nat Cell Biol. 2011 May;13(5):529-40. doi: 10.1038/ncb2224. Epub 2011 Apr 24.


E-cadherin plays a pivotal role in epithelial morphogenesis. It controls the intercellular adhesion required for tissue cohesion and anchors the actomyosin-driven tension needed to change cell shape. In the early Drosophila embryo, Myosin-II (Myo-II) controls the planar polarized remodelling of cell junctions and tissue extension. The E-cadherin distribution is also planar polarized and complementary to the Myosin-II distribution. Here we show that E-cadherin polarity is controlled by the polarized regulation of clathrin- and dynamin-mediated endocytosis. Blocking E-cadherin endocytosis resulted in cell intercalation defects. We delineate a pathway that controls the initiation of E-cadherin endocytosis through the regulation of AP2 and clathrin coat recruitment by E-cadherin. This requires the concerted action of the formin Diaphanous (Dia) and Myosin-II. Their activity is controlled by the guanine exchange factor RhoGEF2, which is planar polarized and absent in non-intercalating regions. Finally, we provide evidence that Dia and Myo-II control the initiation of E-cadherin endocytosis by regulating the lateral clustering of E-cadherin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adherens Junctions
  • Animals
  • Cadherins / metabolism*
  • Cell Cycle Proteins
  • Cell Shape
  • Clathrin / metabolism
  • Drosophila / embryology
  • Drosophila Proteins / physiology*
  • Embryo, Nonmammalian / cytology
  • Endocytosis*
  • Epithelial Cells / cytology*
  • Lymphokines / physiology*
  • Morphogenesis
  • Myosin Type II / physiology*
  • rho GTP-Binding Proteins / physiology*


  • Cadherins
  • Cell Cycle Proteins
  • Clathrin
  • Drosophila Proteins
  • Lymphokines
  • monocyte-macrophage differentiation factor
  • sav protein, Drosophila
  • Myosin Type II
  • rho GTP-Binding Proteins