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Mol Biol Cell January 1, 2009; 20 (1): 78-89.
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Extracellular cleavage of cadherin-11 by ADAM metalloproteases is essential for Xenopus cranial neural crest cell migration.

McCusker C , Cousin H , Neuner R , Alfandari D .

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 beta-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 beta-catenin associated with the cadherin-11 cytoplasmic domain.

PubMed ID: 18946084
PMC ID: PMC2613130
Article link: Mol Biol Cell
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: adam19 adam33 adam9 cad cdh11 ctnnb1 ctnnd1 pacsin2 snai2 sox10 twist1
GO keywords: neural crest cell migration [+]
Morpholinos: adam19 MO1 adam33 MO3 adam9 MO1

Article Images: [+] show captions
References [+] :
Akitaya, Expression of cell adhesion molecules during initiation and cessation of neural crest cell migration. 1992, Pubmed