TY - JOUR
T1 - Lateral clustering of the adhesive ectodomain
T2 - A fundamental determinant of cadherin function
AU - Yap, Alpha S.
AU - Brieher, William M.
AU - Pruschy, Martin
AU - Gumbiner, Barry M.
N1 - Funding Information:
We thank James Marrs (University of Indiana) for the kind gift of anti-cadherin antisera, Noriko Funayama for her skill and endless patience in helping us with our molecular biology, Cara Gottardi, Francois Fagotto, Kris Vleminckx, and Vivian Wong for many incisive discussions and thoughtful comments, and all the members of our laboratories for their support. This research was funded by National Institutes of Health grant GM52717 awarded to B.M.G., the Cancer Support grant NCl-P30-CA-08748, and in part by the Dana Foundation. A.S.Y. acknowledges the support of the National Health and Medical Research Council of Australia and the American Heart Association during the course of this work. M.P. was supported by National Institutes of health grant GM52067 to Stuart L. Schreiber.
PY - 1997/5/1
Y1 - 1997/5/1
N2 - Background: Classical cadherin-based cellular adhesion is mediated by a multi-component protein complex that links the adhesive binding activity of the cadherin ectodomain to the actin cytoskeleton. Despite the importance of cadherins in morphogenesis and development, we know very little about how cells determine and alter cadherin adhesive strength. In this study, we sought to identify specific cellular mechanisms that modulate cadherin function by studying adhesion between cells transfected with Xenopus C-cadherin mutant molecules and substrata coated with the purified ectodomain of C-cadherin. Results: Using the FKBP-FK1012 protein oligomerization system, we found that forced clustering, in cells, of cadherin mutants lacking the cytoplasmic tail significantly increased cellular adhesive strength. Therefore, redistribution of the adhesive binding sites of cells into clusters can influence adhesion independently of other protein interactions mediated by the cadherin cytoplasmic tail. Furthermore, cells transfected with full-length C-cadherin demonstrated dynamic changes in adhesion over time that correlated with clustering but not with changes in the surface expression of C-cadherin or in the composition of the cadherin-catenin complex. The cytoplasmic tail was, however, necessary for clustering of wild-type cadherin. Conclusions: These studies directly demonstrate a fundamental role for lateral clustering in cadherin function. The distribution of cadherin binding sites presented at the cell surface, a cellular property which is regulated by the cadherin cytoplasmic tail, is an important mechanism which modulates cellular adhesion independently of cytoskeletal activity or signalling.
AB - Background: Classical cadherin-based cellular adhesion is mediated by a multi-component protein complex that links the adhesive binding activity of the cadherin ectodomain to the actin cytoskeleton. Despite the importance of cadherins in morphogenesis and development, we know very little about how cells determine and alter cadherin adhesive strength. In this study, we sought to identify specific cellular mechanisms that modulate cadherin function by studying adhesion between cells transfected with Xenopus C-cadherin mutant molecules and substrata coated with the purified ectodomain of C-cadherin. Results: Using the FKBP-FK1012 protein oligomerization system, we found that forced clustering, in cells, of cadherin mutants lacking the cytoplasmic tail significantly increased cellular adhesive strength. Therefore, redistribution of the adhesive binding sites of cells into clusters can influence adhesion independently of other protein interactions mediated by the cadherin cytoplasmic tail. Furthermore, cells transfected with full-length C-cadherin demonstrated dynamic changes in adhesion over time that correlated with clustering but not with changes in the surface expression of C-cadherin or in the composition of the cadherin-catenin complex. The cytoplasmic tail was, however, necessary for clustering of wild-type cadherin. Conclusions: These studies directly demonstrate a fundamental role for lateral clustering in cadherin function. The distribution of cadherin binding sites presented at the cell surface, a cellular property which is regulated by the cadherin cytoplasmic tail, is an important mechanism which modulates cellular adhesion independently of cytoskeletal activity or signalling.
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U2 - 10.1016/S0960-9822(06)00154-0
DO - 10.1016/S0960-9822(06)00154-0
M3 - Article
C2 - 9133345
AN - SCOPUS:0031149109
SN - 0960-9822
VL - 7
SP - 308
EP - 315
JO - Current Biology
JF - Current Biology
IS - 5
ER -