title: ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site.
abstract: 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.
authors.affiliation: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Abbruzzese
authors.affiliation: Department of Cell and Developmental Biology, Karlsruhe Institute of Technology, 76131 Karlsruhe, Germany.|Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR7104, INSERM U964, Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch Cu Strasbourg, France.
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Becker
authors.affiliation: Department of Cell and Developmental Biology, Karlsruhe Institute of Technology, 76131 Karlsruhe, Germany.|Institute for Photon Science and Synchrotron Radiation, Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
authors.forename: Jubin
authors.initials: J
authors.lastname: Kashef
authors.affiliation: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
authors.forename: Dominique
authors.initials: D
authors.lastname: Alfandari
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D002522:Chlorocebus aethiops; D018389:Codon, Nonsense; D057927:Hydrophobic and Hydrophilic Interactions; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology*; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology
chemical_list: D015820:Cadherins; D018389:Codon, Nonsense; D008164:Luminescent Proteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D029867:Xenopus Proteins; C086960:osteoblast cadherin; D051722:ADAM Proteins; C104937:ADAM33 protein, Xenopus
keywords: ADAM; Cadherin; Cell adhesion; Cranial neural crest; Xenopus