title: Axonin-1/TAG-1 mediates cell-cell adhesion by a cis-assisted trans-interaction.
abstract: The neural cell adhesion molecule axonin-1/TAG-1 mediates cell-cell interactions via homophilic and heterophilic contacts. It consists of six Ig and four fibronectin type III domains anchored to the membrane by glycosylphosphatidylinositol. The recently solved crystal structure indicates a module composed of the four N-terminal Ig domains as the contact site between trans-interacting axonin-1 molecules from apposed membranes. Here, we have tested domain-specific monoclonal antibodies for their capacity to interfere with homophilic binding in a cell aggregation assay. The results confirmed the existence of a binding region within the N-terminal Ig domains and identified a second region contributing to homophilic binding on the third and fourth fibronectin domains near the C terminus. The perturbation of each region alone resulted in a complete loss of cell aggregation, suggesting that axonin-1-mediated cell-cell contact results from a cooperative action of two homophilic binding regions. The data support that axonin-1-mediated cell-cell contact is formed by cis-assisted trans-binding. The N-terminal binding regions of axonin-1 establish a linear zipper-like string of trans-interacting axonin-1 molecules alternately provided by the two apposed membranes. The C-terminal binding regions strengthen the cell-cell contact by enhancing the expansion of the linear string into a two-dimensional array via cis-interactions. Cis-assisted trans-binding may be a basic binding mechanism common to many cell adhesion molecules.
authors.affiliation: Institute of Biochemistry, University of Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Kunz
authors.forename: Ruth
authors.initials: R
authors.lastname: Lierheimer
authors.forename: Christoph
authors.initials: C
authors.lastname: Rader
authors.forename: Marianne
authors.initials: M
authors.lastname: Spirig
authors.forename: Urs
authors.initials: U
authors.lastname: Ziegler
authors.forename: Peter
authors.initials: P
authors.lastname: Sonderegger
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002642:Chick Embryo; D058969:Contactin 2; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C548675:Cntn2 protein, mouse; D058969:Contactin 2