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Papers In Press, published online ahead of print November 13, 2007
J. Biol. Chem, 10.1074/jbc.M708044200
Submitted on September 26, 2007
Revised on November 5, 2007
Accepted on November 12, 2007

Two-stage cadherin kinetics require multiple extracellular domains but not the cytoplasmic region

Yuan-Hung Chien, Ning Jiang, Fang Li, Fang Zhang, Cheng Zhu, and Deborah Leckband

Dept. of Chemistry, University of Illinois, Urbana, Illinois 61801

Corresponding Author: leckband{at}uiuc.edu

Micropipette manipulation measurements quantified the pre-steady state binding kinetics between cell pairs, mediated by Xenopus cleavage stage cadherin. The time-dependence of the intercellular binding probability exhibits a fast-forming, low probability binding state which transitions to a slower-forming, high probability state. The biphasic kinetics are independent of the cytoplasmic region, but the transition to the high-probability state requires the third extracellular domain EC3. Deleting either EC3 or EC3-5, or substituting Trp2 for Ala reduces the binding curves to a simple, monophasic rise in binding probability to a limiting plateau, as predicted for a single site binding mechanism. The two-stage cadherin binding process reported here directly parallel previous biophysical studies, and confirms that the cadherin ectodomain governs the initial intercellular adhesion dynamics.


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Q. Shi, Y.-H. Chien, and D. Leckband
Biophysical Properties of Cadherin Bonds Do Not Predict Cell Sorting
J. Biol. Chem., October 17, 2008; 283(42): 28454 - 28463.
[Abstract] [Full Text] [PDF]




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