© The Rockefeller University Press,
0021-9525/1999//687 $5.00
The Journal of Cell Biology, Volume 144, Number 4,
, 1999 687-699
Coupling Assembly of the E-Cadherin/β-Catenin Complex to Efficient Endoplasmic Reticulum Exit and Basal-lateral Membrane Targeting of E-Cadherin in Polarized MDCK Cells
Yih-Tai Chen,
Daniel B. Stewart, and
W. James Nelson
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305-5435
The E-cadherin/catenin complex regulates Ca++-dependent cell–cell adhesion and is localized to the basal-lateral membrane of polarized epithelial cells. Little is known about mechanisms of complex assembly or intracellular trafficking, or how these processes might ultimately regulate adhesion functions of the complex at the cell surface. The cytoplasmic domain of E-cadherin contains two putative basal-lateral sorting motifs, which are homologous to sorting signals in the low density lipoprotein receptor, but an alanine scan across tyrosine residues in these motifs did not affect the fidelity of newly synthesized E-cadherin delivery to the basal-lateral membrane of MDCK cells. Nevertheless, sorting signals are located in the cytoplasmic domain since a chimeric protein (GP2CAD1), comprising the extracellular domain of GP2 (an apical membrane protein) and the transmembrane and cytoplasmic domains of E-cadherin, was efficiently and specifically delivered to the basal-lateral membrane. Systematic deletion and recombination of specific regions of the cytoplasmic domain of GP2CAD1 resulted in delivery of <10% of these newly synthesized proteins to both apical and basal-lateral membrane domains. Significantly, >90% of each mutant protein was retained in the ER. None of these mutants formed a strong interaction with β-catenin, which normally occurs shortly after E-cadherin synthesis. In addition, a simple deletion mutation of E-cadherin that lacks β-catenin binding is also localized intracellularly. Thus, β-catenin binding to the whole cytoplasmic domain of E-cadherin correlates with efficient and targeted delivery of E-cadherin to the lateral plasma membrane. In this capacity, we suggest that β-catenin acts as a chauffeur, to facilitate transport of E-cadherin out of the ER and the plasma membrane.
Key Words: polarity epithelia adhesion protein targeting membrane domains
Abbreviations used in this paper: aa, amino acids; arm, armadillo; CYT, cytoplasmic; endo H, endoglycosidase H; GFP, green fluorescent protein; GPI, glycosylphosphotidylinositol; LDL, low density lipoprotein; TER, transepithelial electrical resistance; TM, transmembrane.
Address correspondence to W. James Nelson, Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305-5435. Tel.: (650) 725-7596. Fax: (650) 498-5286. E-mail: wjnelson{at}leland.stanford.edu
Yih-Tai Chen's current address is Cellomics, Inc., 635 William Pitt Way, Pittsburgh, PA 15238.

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-
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-
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-
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-
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-
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-
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(2004). Continuous association of cadherin with {beta}-catenin requires the non-receptor tyrosine-kinase Fer. J. Cell Sci.
117: 3207-3219
[Abstract]
[Full Text]
-
Brown, A., Muth, T., Caplan, M.
(2004). The COOH-terminal tail of the GAT-2 GABA transporter contains a novel motif that plays a role in basolateral targeting. Am. J. Physiol. Cell Physiol.
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[Full Text]
-
Gottardi, C. J., Gumbiner, B. M.
(2004). Role for ICAT in {beta}-catenin-dependent nuclear signaling and cadherin functions. Am. J. Physiol. Cell Physiol.
286: C747-C756
[Abstract]
[Full Text]
-
Murray, R. Z., Jolly, L. A., Wood, S. A.
(2004). The FAM Deubiquitylating Enzyme Localizes to Multiple Points of Protein Trafficking in Epithelia, where It Associates with E-cadherin and {beta}-catenin. Mol. Biol. Cell
15: 1591-1599
[Abstract]
[Full Text]
-
Faux, M. C., Ross, J. L., Meeker, C., Johns, T., Ji, H., Simpson, R. J., Layton, M. J., Burgess, A. W.
(2004). Restoration of full-length adenomatous polyposis coli (APC) protein in a colon cancer cell line enhances cell adhesion. J. Cell Sci.
117: 427-439
[Abstract]
[Full Text]
-
Peifer, M., Yap, A. S.
(2003). Traffic control: p120-catenin acts as a gatekeeper to control the fate of classical cadherins in mammalian cells. JCB
163: 437-440
[Abstract]
[Full Text]
-
DeBellefeuille, S., Hermo, L., Gregory, M., Dufresne, J., Cyr, D. G.
(2003). Catenins in the Rat Epididymis: Their Expression and Regulation in Adulthood and during Postnatal Development. Endocrinology
144: 5040-5049
[Abstract]
[Full Text]
-
Miranda, K. C., Joseph, S. R., Yap, A. S., Teasdale, R. D., Stow, J. L.
(2003). Contextual Binding of p120ctn to E-cadherin at the Basolateral Plasma Membrane in Polarized Epithelia. J. Biol. Chem.
278: 43480-43488
[Abstract]
[Full Text]
-
Sabe, H.
(2003). Requirement for Arf6 in Cell Adhesion, Migration, and Cancer Cell Invasion. J Biochem
134: 485-489
[Abstract]
[Full Text]
-
Katafiasz, B. J., Nieman, M. T., Wheelock, M. J., Johnson, K. R.
(2003). Characterization of Cadherin-24, a Novel Alternatively Spliced Type II Cadherin. J. Biol. Chem.
278: 27513-27519
[Abstract]
[Full Text]
-
Fasolini, M., Wu, X., Flocco, M., Trosset, J.-Y., Oppermann, U., Knapp, S.
(2003). Hot Spots in Tcf4 for the Interaction with {beta}-Catenin. J. Biol. Chem.
278: 21092-21098
[Abstract]
[Full Text]
-
Xiao, K., Allison, D. F., Kottke, M. D., Summers, S., Sorescu, G. P., Faundez, V., Kowalczyk, A. P.
(2003). Mechanisms of VE-cadherin Processing and Degradation in Microvascular Endothelial Cells. J. Biol. Chem.
278: 19199-19208
[Abstract]
[Full Text]
-
Xu, G., Arregui, C., Lilien, J., Balsamo, J.
(2002). PTP1B Modulates the Association of beta -Catenin with N-cadherin through Binding to an Adjacent and Partially Overlapping Target Site. J. Biol. Chem.
277: 49989-49997
[Abstract]
[Full Text]
-
Schreider, C., Peignon, G., Thenet, S., Chambaz, J., Pincon-Raymond, M.
(2002). Integrin-mediated functional polarization of Caco-2 cells through E-cadherin--actin complexes. J. Cell Sci.
115: 543-552
[Abstract]
[Full Text]
-
Marion, S., Robert, F., Crepieux, P., Martinat, N., Troispoux, C., Guillou, F., Reiter, E.
(2002). G Protein-Coupled Receptor Kinases and Beta Arrestins Are Relocalized and Attenuate Cyclic 3',5'-Adenosine Monophosphate Response to Follicle-Stimulating Hormone in Rat Primary Sertoli Cells. Biol. Reprod.
66: 70-76
[Abstract]
[Full Text]
-
Jolimay, N., Franck, L., Langlois, X., Hamon, M., Darmon, M.
(2000). Dominant Role of the Cytosolic C-Terminal Domain of the Rat 5-HT1B Receptor in Axonal-Apical Targeting. J. Neurosci.
20: 9111-9118
[Abstract]
[Full Text]
-
Mo, C., Schneeberger, E. E., Arvin, A. M.
(2000). Glycoprotein E of Varicella-Zoster Virus Enhances Cell-Cell Contact in Polarized Epithelial Cells. J. Virol.
74: 11377-11387
[Abstract]
[Full Text]
-
Groten, T., Kreienberg, R., Fialka, I., Huber, L., Wedlich, D.
(2000). Altered subcellular distribution of cadherin-5 in endothelial cells caused by the serum of pre-eclamptic patients. Mol Hum Reprod
6: 1027-1032
[Abstract]
[Full Text]
-
Lecuit, M., Hurme, R., Pizarro-Cerda, J., Ohayon, H., Geiger, B., Cossart, P.
(2000). A role for alpha - and beta -catenins in bacterial uptake. Proc. Natl. Acad. Sci. USA
97: 10008-10013
[Abstract]
[Full Text]
-
Charron, A. J., Nakamura, S., Bacallao, R., Wandinger-Ness, A.
(2000). Compromised Cytoarchitecture and Polarized Trafficking in Autosomal Dominant Polycystic Kidney Disease Cells. JCB
149: 111-124
[Abstract]
[Full Text]
-
Thoreson, M. A., Anastasiadis, P. Z., Daniel, J. M., Ireton, R. C., Wheelock, M. J., Johnson, K. R., Hummingbird, D. K., Reynolds, A. B.
(2000). Selective Uncoupling of P120ctn from E-Cadherin Disrupts Strong Adhesion. JCB
148: 189-202
[Abstract]
[Full Text]
-
De Matteis, M., Morrow, J.
(2000). Spectrin tethers and mesh in the biosynthetic pathway. J. Cell Sci.
113: 2331-2343
[Abstract]
-
Martel, V, Vignoud, L, Dupe, S, Frachet, P, Block, M., Albiges-Rizo, C
(2000). Talin controls the exit of the integrin alpha 5 beta 1 from an early compartment of the secretory pathway. J. Cell Sci.
113: 1951-1961
[Abstract]
-
Ellgaard, L., Molinari, M., Helenius, A.
(1999). Setting the Standards: Quality Control in the Secretory Pathway. Science
286: 1882-1888
[Abstract]
[Full Text]
-
Quinlan, M. P., Hyatt, J. L.
(1999). Establishment of the Circumferential Actin Filament Network Is a Prerequisite for Localization of the Cadherin-Catenin Complex in Epithelial Cells. Cell Growth Differ.
10: 839-854
[Abstract]
[Full Text]
-
Le, T. L., Yap, A. S., Stow, J. L.
(1999). Recycling of E-Cadherin: A Potential Mechanism for Regulating Cadherin Dynamics. JCB
146: 219-232
[Abstract]
[Full Text]
-
Stewart, D. B., Barth, A. I. M., Nelson, W. J.
(2000). Differential Regulation of Endogenous Cadherin Expression in Madin-Darby Canine Kidney Cells by Cell-Cell Adhesion and Activation of beta -Catenin Signaling. J. Biol. Chem.
275: 20707-20716
[Abstract]
[Full Text]
-
Huber, A. H., Stewart, D. B., Laurents, D. V., Nelson, W. J., Weis, W. I.
(2001). The Cadherin Cytoplasmic Domain Is Unstructured in the Absence of beta -Catenin. A POSSIBLE MECHANISM FOR REGULATING CADHERIN TURNOVER. J. Biol. Chem.
276: 12301-12309
[Abstract]
[Full Text]
-
Keller, S. H., Lindstrom, J., Ellisman, M., Taylor, P.
(2001). Adjacent Basic Amino Acid Residues Recognized by the COP I Complex and Ubiquitination Govern Endoplasmic Reticulum to Cell Surface Trafficking of the Nicotinic Acetylcholine Receptor alpha -Subunit. J. Biol. Chem.
276: 18384-18391
[Abstract]
[Full Text]
-
Miranda, K. C., Khromykh, T., Christy, P., Le, T. L., Gottardi, C. J., Yap, A. S., Stow, J. L., Teasdale, R. D.
(2001). A Dileucine Motif Targets E-cadherin to the Basolateral Cell Surface in Madin-Darby Canine Kidney and LLC-PK1 Epithelial Cells. J. Biol. Chem.
276: 22565-22572
[Abstract]
[Full Text]