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Originally published as MBC in Press, 10.1091/mbc.E08-05-0535 on October 22, 2008

Vol. 20, Issue 1, 78-89, January 1, 2009

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Extracellular Cleavage of Cadherin-11 by ADAM Metalloproteases Is Essential for Xenopus Cranial Neural Crest Cell Migration

Catherine McCusker, Hélène Cousin, Russell Neuner, and Dominique Alfandari

Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003

Submitted May 30, 2008; Revised September 19, 2008; Accepted October 9, 2008
Monitoring Editor: Richard O. Hynes

Cell adhesion molecules such as cadherins alternate their expression throughout cranial neural crest (CNC) development, yet our understanding of the role of these molecules during CNC migration remains incomplete. The "mesenchymal" cadherin-11 is expressed in the CNC during migration yet prevents migration when overexpressed in the embryo, suggesting that a defined level of cadherin-11–mediated cell adhesion is required for migration. Here we show that members of the meltrin subfamily of ADAM metalloproteases cleave the extracellular domain of cadherin-11 during CNC migration. We show that a fragment corresponding to the putative shed form of cadherin-11 retains biological activity by promoting CNC migration in vivo, in a non-cell–autonomous manner. Additionally, cleavage of cadherin-11 does not affect binding to β-catenin and downstream signaling events. We propose that ADAM cleavage of cadherin-11 promotes migration by modifying its ability to support cell–cell adhesion while maintaining the membrane-bound pool of β-catenin associated with the cadherin-11 cytoplasmic domain.


This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08-05-0535) on October 22, 2008.

Address correspondence to: Dominique Alfandari (alfandar{at}vasci.umass.edu)




This article has been cited by other articles:


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J. Kashef, A. Kohler, S. Kuriyama, D. Alfandari, R. Mayor, and D. Wedlich
Cadherin-11 regulates protrusive activity in Xenopus cranial neural crest cells upstream of Trio and the small GTPases
Genes & Dev., June 15, 2009; 23(12): 1393 - 1398.
[Abstract] [Full Text] [PDF]




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