title: Spatial regulation of Dia and Myosin-II by RhoGEF2 controls initiation of E-cadherin endocytosis during epithelial morphogenesis.
abstract: 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.
authors.affiliation: IBDML, UMR6216 CNRS-Université de la Méditerranée, Campus de Luminy, case 907. 13288 Marseille Cedex 09, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Levayer
authors.forename: Anne
authors.initials: A
authors.lastname: Pelissier-Monier
authors.forename: Thomas
authors.initials: T
authors.lastname: Lecuit
mesh_terms: D022005:Adherens Junctions; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D048430:Cell Shape; D002966:Clathrin / Q000378:metabolism; D004330:Drosophila / Q000196:embryology; D029721:Drosophila Proteins / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000166:cytology; D004705:Endocytosis; D004847:Epithelial Cells / Q000166:cytology*; D008222:Lymphokines / Q000502:physiology*; D009024:Morphogenesis; D024462:Myosin Type II / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000502:physiology*
chemical_list: D015820:Cadherins; D018797:Cell Cycle Proteins; D002966:Clathrin; D029721:Drosophila Proteins; D008222:Lymphokines; C050979:monocyte-macrophage differentiation factor; C465504:sav protein, Drosophila; D024462:Myosin Type II; D020741:rho GTP-Binding Proteins