ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site

• Published in: Developmental biology Vol. 415; no. 2; pp. 383 - 390
• Main Authors: Abbruzzese, Genevieve, Becker, Sarah F., Kashef, Jubin, Alfandari, Dominique
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.07.2016; Elsevier
• Subjects: ADAM; ADAM Proteins - metabolism; Animals; Binding Sites; Cadherin; Cadherins - genetics; Cadherins - metabolism; Cell Adhesion; Cell Movement - drug effects; Cellular Biology; Cercopithecus aethiops; Codon, Nonsense; COS Cells; Cranial neural crest; Hydrophobic and Hydrophilic Interactions; Life Sciences; Luminescent Proteins - analysis; Luminescent Proteins - genetics; Membrane Proteins - metabolism; Neural Crest - cytology; Organ Culture Techniques; Peptide Fragments - pharmacology; Peptide Fragments - physiology; Protein Binding; Protein Processing, Post-Translational; Recombinant Proteins - metabolism; Structure-Activity Relationship; Transfection; Xenopus; Xenopus laevis - embryology; Xenopus Proteins - genetics; Xenopus Proteins - metabolism; Xenopus; ADAM; Cadherin; Cranial neural crest; Cell adhesion
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2015.07.018

The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell–cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo. •A non-cleavable form of cadherin-11 does not support CNC migration.•Shed cadherin-11 promotes cell migration independently of the homophylic site.•ADAM13 overexpression inhibit contact inhibition of locomotion.