title: Antagonistic and agonistic effects of an extracellular fragment of nectin on formation of E-cadherin-based cell-cell adhesion.
abstract: BACKGROUND
  Nectin is a Ca2+-independent immunoglobulin-like cell-cell adhesion molecule at the E-cadherin-based cell-cell adherens junctions (AJs), and comprises a family consisting of four members, nectin-1, -2, -3, and -4. Nectin and E-cadherin are associated with afadin and alpha-catenin, actin filament (F-actin)-binding proteins connecting respective adhesion molecules to the actin cytoskeleton, but the role of nectin in the formation of the E-cadherin-based cell-cell AJs has not yet been fully understood. To obtain evidence for this role of nectin, we attempted to develop an antagonist and/or agonist of nectin.
  
  
  RESULTS
  We made a recombinant extracellular fragment of nectin-3 (Nef-3). Nef-3 trans-interacted with cellular nectin-1 and thereby diminished the formation of the nectin-1-based cell-cell adhesion. This resulted in a reduction of the formation of the E-cadherin-based cell-cell adhesion in L fibroblasts stably expressing both exogenous nectin-1alpha and E-cadherin (nectin-1-EL cells) and MDCK cells stably expressing exogenous nectin-1alpha (nectin-1-MDCK cells). This antagonistic effect of Nef-3 was also observed in L cells stably expressing exogenous E-cadherin alone (EL cells) and wild-type MDCK cells. Conversely, Nef-3 coated on microbeads first recruited the nectin-afadin complex and then the E-cadherin-catenin complex to the bead-cell contact sites in nectin-1-EL and nectin-1-MDCK cells.
  
  
  CONCLUSIONS
  These results suggest that nectin is necessary and sufficient for the recruitment of E-cadherin to the nectin-based cell-cell adhesion sites and involved in the formation of E-cadherin-based cell-cell AJs.
authors.affiliation: Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Honda
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimizu
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kawakatsu
authors.forename: Masato
authors.initials: M
authors.lastname: Yasumi
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Shingai
authors.forename: Atsunori
authors.initials: A
authors.lastname: Fukuhara
authors.forename: Kumi
authors.initials: K
authors.lastname: Ozaki-Kuroda
authors.forename: Kenji
authors.initials: K
authors.lastname: Irie
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: D000818:Animals; D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000494:pharmacology*; D002478:Cells, Cultured; D004285:Dogs; D007365:Intercellular Junctions / Q000187:drug effects* / Q000502:physiology; D008840:Microfilament Proteins / Q000378:metabolism; D008954:Models, Biological; D000075983:Nectins; D010446:Peptide Fragments / Q000494:pharmacology
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D000075983:Nectins; D010446:Peptide Fragments; C108835:afadin