Binding to cadherins antagonizes the signaling activity of beta-catenin during axis formation in Xenopus

被引:286
作者
Fagotto, F [1 ]
Funayama, N [1 ]
Gluck, U [1 ]
Gumbiner, BM [1 ]
机构
[1] MEM SLOAN KETTERING CANC CTR,CELLULAR BIOCHEM & BIOPHYS PROGRAM,NEW YORK,NY 10021
关键词
D O I
10.1083/jcb.132.6.1105
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
beta-Catenin, a cytoplasmic protein known for its association with cadherin cell adhesion molecules, is also part of a signaling cascade involved in embryonic patterning processes such as the determination of the dorsoventral axis in Xenopus and determination of segment polarity in Drosophila. Previous studies suggest that increased cytoplasmic levels of beta-catenin correlate with signaling, raising questions about the need for interaction with cadherins in this process. We have tested the role of the beta-catenin-cadherin interaction in axis formation. Using beta-catenin deletion mutants, we demonstrate that significant binding to cadherins can be eliminated without affecting the signaling activity. Also, depletion of the soluble, cytosolic pool of beta-catenin by binding to overexpressed C-cadherin completely inhibited beta-catenin-inducing activity. We conclude that binding to cadherins is not required for beta-catenin signaling, and therefore the signaling function of beta-catenin is independent of its role in cell adhesion. Moreover, because beta-catenin signaling is antagonized by binding to cadherins, we suggest that cadherins can act as regulators of the intracellular beta-catenin signaling pathway.
引用
收藏
页码:1105 / 1114
页数:10
相关论文
共 42 条
[1]   EXPRESSION OF A DOMINANT NEGATIVE MUTANT OF THE FGF RECEPTOR DISRUPTS MESODERM FORMATION IN XENOPUS EMBRYOS [J].
AMAYA, E ;
MUSCI, TJ ;
KIRSCHNER, MW .
CELL, 1991, 66 (02) :257-270
[2]   EXPRESSION OF WNT-1 IN PC12 CELLS RESULTS IN MODULATION OF PLAKOGLOBIN AND E-CADHERIN AND INCREASED CELLULAR ADHESION [J].
BRADLEY, RS ;
COWIN, P ;
BROWN, AMC .
JOURNAL OF CELL BIOLOGY, 1993, 123 (06) :1857-1865
[3]   REGULATION OF C-CADHERIN FUNCTION DURING ACTIVIN INDUCED MORPHOGENESIS OF XENOPUS ANIMAL CAPS [J].
BRIEHER, WM ;
GUMBINER, BM .
JOURNAL OF CELL BIOLOGY, 1994, 126 (02) :519-527
[4]   MORPHOREGULATORY ACTIVITIES OF NCAM AND N-CADHERIN CAN BE ACCOUNTED FOR BY G PROTEIN-DEPENDENT ACTIVATION OF L-TYPE AND N-TYPE NEURONAL CA2+ CHANNELS [J].
DOHERTY, P ;
ASHTON, SV ;
MOORE, SE ;
WALSH, FS .
CELL, 1991, 67 (01) :21-33
[5]  
FAGOTTO F, 1994, DEVELOPMENT, V120, P3667
[6]  
FLEMING TP, 1988, ANNU REV CELL BIOL, V4, P459, DOI 10.1146/annurev.cellbio.4.1.459
[7]   EMBRYONIC AXIS INDUCTION BY THE ARMADILLO REPEAT DOMAIN OF BETA-CATENIN - EVIDENCE FOR INTRACELLULAR SIGNALING [J].
FUNAYAMA, N ;
FAGOTTO, F ;
MCCREA, P ;
GUMBINER, BM .
JOURNAL OF CELL BIOLOGY, 1995, 128 (05) :959-968
[8]   BETA-CATENIN HAS WNT-LIKE ACTIVITY AND MIMICS THE NIEUWKOOP SIGNALING CENTER IN XENOPUS DORSAL-VENTRAL PATTERNING [J].
GUGER, KA ;
GUMBINER, BM .
DEVELOPMENTAL BIOLOGY, 1995, 172 (01) :115-125
[9]   THE ROLE OF THE CELL-ADHESION MOLECULE UVOMORULIN IN THE FORMATION AND MAINTENANCE OF THE EPITHELIAL JUNCTIONAL COMPLEX [J].
GUMBINER, B ;
STEVENSON, B ;
GRIMALDI, A .
JOURNAL OF CELL BIOLOGY, 1988, 107 (04) :1575-1587
[10]   SIGNAL-TRANSDUCTION BY BETA-CATENIN [J].
GUMBINER, BM .
CURRENT OPINION IN CELL BIOLOGY, 1995, 7 (05) :634-640