Drosophila Cip4 and WASp define a branch of the Cdc42-Par6-aPKC pathway regulating E-cadherin endocytosis

Curr Biol. 2008 Nov 11;18(21):1639-48. doi: 10.1016/j.cub.2008.09.063. Epub 2008 Oct 30.

Abstract

Background: Integral to the function and morphology of the epithelium is the lattice of cell-cell junctions known as adherens junctions (AJs). AJ stability and plasticity relies on E-Cadherin exocytosis and endocytosis. A mechanism regulating E-Cadherin (E-Cad) exocytosis to the AJs has implicated proteins of the exocyst complex, but mechanisms regulating E-Cad endocytosis from the AJs remain less well understood.

Results: Here we show that Cdc42, Par6, or aPKC loss of function is accompanied by the accumulation of apical E-Cad intracellular punctate structures and the disruption of AJs in Drosophila epithelial cells. These punctate structures derive from large and malformed endocytic vesicles that emanate from the AJs; a phenotype that is also observed upon blocking vesicle scission in dynamin mutant cells. We demonstrate that the Drosophila Cdc42-interacting protein 4 (Cip4) is a Cdc42 effector that interacts with Dynamin and the Arp2/3 activator WASp in Drosophila. Accordingly, Cip4, WASp, or Arp2/3 loss of function also results in defective E-Cadherin endocytosis.

Conclusion: Altogether our results show that Cdc42 functions with Par6 and aPKC to regulate E-Cad endocytosis and define Cip4 and WASp as regulators of the early E-Cad endocytic events in epithelial tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / metabolism
  • Actins / metabolism
  • Adherens Junctions / metabolism*
  • Animals
  • Cadherins / metabolism*
  • Carrier Proteins / metabolism
  • Drosophila / metabolism
  • Drosophila Proteins / metabolism*
  • Dynamins / metabolism
  • Endocytosis*
  • Epithelial Cells / metabolism
  • Protein Kinase C / metabolism*
  • Wiskott-Aldrich Syndrome Protein / metabolism
  • cdc42 GTP-Binding Protein / metabolism*

Substances

  • Actin-Related Protein 2-3 Complex
  • Actins
  • Cadherins
  • Carrier Proteins
  • Cip4 protein, Drosophila
  • Drosophila Proteins
  • WASp protein, Drosophila
  • Wiskott-Aldrich Syndrome Protein
  • PKC-3 protein
  • Par-6 protein, Drosophila
  • Protein Kinase C
  • cdc42 GTP-Binding Protein
  • Dynamins