ARF6-GTP recruits Nm23-H1 to facilitate dynamin-mediated endocytosis during adherens junctions disassembly.
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.
Palacios
Felipe
F
Department of Biological Sciences and the Walther Cancer Institute, University of Notre Dame, Notre Dame, IN, USA.
Schweitzer
Jill K
JK
Boshans
Rita L
RL
D'Souza-Schorey
Crislyn
C
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000502:physiology*; D022005:Adherens Junctions / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D016764:Cell Polarity; D004285:Dogs; D004705:Endocytosis / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000502:physiology*; D020559:Monomeric GTP-Binding Proteins / Q000502:physiology*; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D014157:Transcription Factors / Q000502:physiology*
D000089982:ADP-Ribosylation Factor 6; D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; D006160:Guanosine Triphosphate; D009701:Nucleoside-Diphosphate Kinase; D020727:ADP-Ribosylation Factors; D020559:Monomeric GTP-Binding Proteins