Trans-interactions of nectins induce formation of filopodia and Lamellipodia through the respective activation of Cdc42 and Rac small G proteins.
Nectins and afadin constitute a novel cell-cell adhesion system that plays a cooperative role with cadherins in the organization of adherens junctions (AJs). Nectins are Ca(2+)-independent immunoglobulin-like cell-cell adhesion molecules, and afadin is a nectin- and actin filament-binding protein that connects nectins to the actin cytoskeleton. Rac and Cdc42 small G proteins have been implicated in the organization of AJs, but their modes of action remain unknown. The trans-interaction of E-cadherin has recently been shown to induce the activation of Rac, but not that of Cdc42. We show here that the trans-interactions of nectins induce the formation of filopodia and lamellipodia through the respective activation of Cdc42 and Rac. The Cdc42 activation is necessary, but not sufficient, for the Rac-induced formation of lamellipodia, whereas the Rac activation is not necessary for the Cdc42-induced formation of filopodia. These effects of nectins require their cytoplasmic tail but not their association with afadin. We propose here the functional relationship between nectins and the small G proteins in the organization of AJs.
Kawakatsu
Tomomi
T
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
Shimizu
Kazuya
K
Honda
Tomoyuki
T
Fukuhara
Tatsuro
T
Hoshino
Takashi
T
Takai
Yoshimi
Y
D000818:Animals; D015820:Cadherins / Q000502:physiology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D006801:Humans; D007739:L Cells; D051379:Mice; D008855:Microscopy, Electron, Scanning; D000075983:Nectins; D011554:Pseudopodia / Q000648:ultrastructure*; D051381:Rats; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
D015820:Cadherins; D015815:Cell Adhesion Molecules; D000075983:Nectins; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins