ARF6-GTP recruits Nm23-H1 to facilitate dynamin-mediated endocytosis during adherens junctions disassembly

Nat Cell Biol. 2002 Dec;4(12):929-36. doi: 10.1038/ncb881.


ARF6-regulated endocytosis of E-cadherin is essential during the disassembly of adherens junctions in epithelial cells. Here, we show that activation of ARF6 promotes clathrin-dependent internalization of E-cadherin and caveolae at the basolateral cell surface. Furthermore, we demonstrate that ARF6-GTP, a constitutively activate form of ARF6, interacts with and recruits Nm23-H1, a nucleoside diphosphate (NDP) kinase that provides a source of GTP for dynamin-dependent fission of coated vesicles during endocytosis. Finally, we show that ARF6-mediated recruitment of Nm-23-H1 to cell junctions is accompanied by a decrease in the cellular levels of Rac1-GTP, consistent with previous findings that Nm23-H1 down-regulates activation of Rac1. These studies provide a molecular basis for ARF6 function in polarized epithelia during adherens junction disassembly.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ADP-Ribosylation Factors / physiology*
  • Adherens Junctions / physiology*
  • Animals
  • Cell Line
  • Cell Movement
  • Cell Polarity
  • Dogs
  • Endocytosis / physiology*
  • Epithelial Cells / cytology
  • Epithelial Cells / physiology*
  • Guanosine Triphosphate / physiology*
  • Monomeric GTP-Binding Proteins / physiology*
  • NM23 Nucleoside Diphosphate Kinases
  • Nucleoside-Diphosphate Kinase*
  • Transcription Factors / physiology*


  • NM23 Nucleoside Diphosphate Kinases
  • Transcription Factors
  • Guanosine Triphosphate
  • Nucleoside-Diphosphate Kinase
  • ADP-Ribosylation Factors
  • ADP-ribosylation factor 6
  • Monomeric GTP-Binding Proteins