A novel role of nectins in inhibition of the E-cadherin-induced activation of Rac and formation of cell-cell adherens junctions.
Nectins are Ca(2+)-independent immunoglobulin (Ig)-like cell-cell adhesion molecules. The trans-interactions of nectins recruit cadherins to the nectin-based cell-cell adhesion, resulting in formation of cell-cell adherens junctions (AJs) in epithelial cells and fibroblasts. The trans-interaction of E-cadherin induces activation of Rac small G protein, whereas the trans-interactions of nectins induce activation of not only Rac but also Cdc42 small G protein. We showed by the fluorescent resonance energy transfer (FRET) imaging that the trans-interaction of E-cadherin induced dynamic activation and inactivation of Rac, which led to dynamic formation and retraction of lamellipodia. Moreover, we found here that the nectins, which did not trans-interact with other nectins (non-trans-interacting nectins), inhibited the E-cadherin-induced activation of Rac and reduced the velocity of the formation of the E-cadherin-based cell-cell AJs. The inhibitory effect of non-trans-interacting nectins was suppressed by the activation of Cdc42 induced by the trans-interactions of nectins. These results indicate a novel role of nectins in regulation of the E-cadherin-induced activation of Rac and formation of cell-cell AJs.
Hoshino
Takashi
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
Kawakatsu
Tomomi
T
Fukuyama
Taihei
T
Nakamura
Takeshi
T
Matsuda
Michiyuki
M
Takai
Yoshimi
Y
D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D015693:Gene Products, nef / Q000378:metabolism; D007739:L Cells; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D000075983:Nectins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
D015820:Cadherins; D015815:Cell Adhesion Molecules; D015693:Gene Products, nef; D008840:Microfilament Proteins; D000075983:Nectins; D019869:Phosphatidylinositol 3-Kinases; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins