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Journal of Cell Science, Vol 114, Issue 10 1829-1838, Copyright © 2001 by Company of Biologists
JOURNAL ARTICLES |
M Nakagawa, M Fukata, M Yamaga, N Itoh and K Kaibuchi
Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma 630-0101, Japan. kaibuchi@bs.aist-nara.ac.jp
Rac1, a member of the &Rgr; family small GTPases, regulates E-cadherin-mediated cell-cell adhesion. However, it remains to be clarified how the localization and activation of Rac1 are regulated at sites of cell-cell contact. Here, using enhanced green fluorescence protein (EGFP)-tagged Rac1, we demonstrate that EGFP-Rac1 is colocalized with E-cadherin at sites of cell-cell contact and translocates to the cytosol during disruption of E-cadherin-mediated cell-cell adhesion by Ca(2+) chelation. Re-establishment of cell-cell adhesion by restoration of Ca(2)(+) caused EGFP-Rac1 to become relocalized, together with E-cadherin, at sites of cell-cell contact. Engagement of E-cadherin to the apical membrane by anti-E-cadherin antibody (ECCD-2) recruited EGFP-Rac1. We also investigated whether E-cadherin-mediated cell-cell adhesion induced Rac1 activation by measuring the amounts of GTP-bound Rac1 based on its specific binding to the Cdc42/Rac1 interactive binding region of p21-activated kinase. The formation of E-cadherin-mediated cell-cell adhesion induced Rac1 activation. This activation was inhibited by treatment of cells with a neutralizing antibody (DECMA-1) against E-cadherin, or with wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase). IQGAP1, an effector of Rac1, and EGFP-Rac1 behaved in a similar manner during the formation of E-cadherin-mediated cell-cell adhesion. Rac1 activation was also confirmed by measuring the amounts of coimmunoprecipitated Rac1 with IQGAP1 during the establishment of cell-cell adhesion. Taken together, these results suggest that Rac1 is recruited at sites of E-cadherin-mediated cell-cell adhesion and then activated, possibly through PI 3-kinase. http://www/biologists.com/JCS/movies/jcs2094.html
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M. Betson, E. Lozano, J. Zhang, and V. M. M. Braga Rac Activation upon Cell-Cell Contact Formation Is Dependent on Signaling from the Epidermal Growth Factor Receptor J. Biol. Chem., September 27, 2002; 277(40): 36962 - 36969. [Abstract] [Full Text] [PDF]
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R. Ruiz-Velasco, C. C. Lanning, and C. L. Williams The Activation of Rac1 by M3 Muscarinic Acetylcholine Receptors Involves the Translocation of Rac1 and IQGAP1 to Cell Junctions and Changes in the Composition of Protein Complexes Containing Rac1, IQGAP1, and Actin J. Biol. Chem., August 30, 2002; 277(36): 33081 - 33091. [Abstract] [Full Text] [PDF]
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 L. Van Aelst and M. Symons Role of Rho family GTPases in epithelial morphogenesis Genes & Dev., May 1, 2002; 16(9): 1032 - 1054. [Full Text] [PDF]
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M. Lambert, D. Choquet, and R.-M. Mege Dynamics of ligand-induced, Rac1-dependent anchoring of cadherins to the actin cytoskeleton J. Cell Biol., April 29, 2002; 157(3): 469 - 479. [Abstract] [Full Text] [PDF]
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M. G. Lampugnani, A. Zanetti, F. Breviario, G. Balconi, F. Orsenigo, M. Corada, R. Spagnuolo, M. Betson, V. Braga, and E. Dejana VE-Cadherin Regulates Endothelial Actin Activating Rac and Increasing Membrane Association of Tiam Mol. Biol. Cell, April 1, 2002; 13(4): 1175 - 1189. [Abstract] [Full Text] [PDF]
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P. Laprise, P. Chailler, M. Houde, J.-F. Beaulieu, M.-J. Boucher, and N. Rivard Phosphatidylinositol 3-Kinase Controls Human Intestinal Epithelial Cell Differentiation by Promoting Adherens Junction Assembly and p38 MAPK Activation J. Biol. Chem., March 1, 2002; 277(10): 8226 - 8234. [Abstract] [Full Text] [PDF]
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N. K. Noren, C. M. Niessen, B. M. Gumbiner, and K. Burridge Cadherin Engagement Regulates Rho family GTPases J. Biol. Chem., August 31, 2001; 276(36): 33305 - 33308. [Abstract] [Full Text] [PDF]
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E. M. Kovacs, R. G. Ali, A. J. McCormack, and A. S. Yap E-cadherin Homophilic Ligation Directly Signals through Rac and Phosphatidylinositol 3-Kinase to Regulate Adhesive Contacts J. Biol. Chem., February 15, 2002; 277(8): 6708 - 6718. [Abstract] [Full Text] [PDF]
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M. Lambert, D. Choquet, and R.-M. Mege Dynamics of ligand-induced, Rac1-dependent anchoring of cadherins to the actin cytoskeleton J. Cell Biol., April 29, 2002; 157(3): 469 - 479. [Abstract] [Full Text] [PDF]
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