Endocytosis of E-cadherin regulated by Rac and Cdc42 small G proteins through IQGAP1 and actin filaments.
E-cadherin is a key cell-cell adhesion molecule at adherens junctions (AJs) and undergoes endocytosis when AJs are disrupted by the action of extracellular signals. To elucidate the mechanism of this endocytosis, we developed here a new cell-free assay system for this reaction using the AJ-enriched fraction from rat liver. We found here that non-trans-interacting, but not trans-interacting, E-cadherin underwent endocytosis in a clathrin-dependent manner. The endocytosis of trans-interacting E-cadherin was inhibited by Rac and Cdc42 small G proteins, which were activated by trans-interacting E-cadherin or trans-interacting nectins, which are known to induce the formation of AJs in cooperation with E-cadherin. This inhibition was mediated by reorganization of the actin cytoskeleton by Rac and Cdc42 through IQGAP1, an actin filament-binding protein and a downstream target of Rac and Cdc42. These results indicate the important role of the Rac/Cdc42-IQGAP1 system in the dynamic organization and maintenance of the E-cadherin-based AJs.
Izumi
Genkichi
G
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan.
Sakisaka
Toshiaki
T
Baba
Takeshi
T
Tanaka
Shintaro
S
Morimoto
Koji
K
Takai
Yoshimi
Y
D008841:Actin Cytoskeleton; D022005:Adherens Junctions; D000818:Animals; D001921:Brain; D015820:Cadherins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002474:Cell-Free System; D022163:Clathrin-Coated Vesicles; D004705:Endocytosis; D019204:GTP-Binding Proteins / Q000502:physiology; D008099:Liver; D051381:Rats; D020764:cdc42 GTP-Binding Protein / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000502:physiology*; D020703:ras GTPase-Activating Proteins
D015820:Cadherins; D002352:Carrier Proteins; C101203:IQ motif containing GTPase activating protein 1; D020703:ras GTPase-Activating Proteins; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins