Abstract
The nectin cell adhesion molecules interact in trans with each other through their extracellular regions and with afadin through their cytoplasmic tails, forming adherens junctions in cooperation with cadherins. In a single cell, Necl-5 (nectin-like molecule-5) localizes at the leading edge and regulates directional cell movement in response to a chemoattractant. In such a single cell, afadin also localizes at the leading edge without interacting with nectins or Necl-5. It remains unknown how the nectin-nectin and nectin-afadin interactions are initiated when moving cells contact each other to initiate the formation of adherens junctions. We show here that the Necl-5-nectin interaction induced by cell-cell contact enhances the nectin-afadin interaction. This interaction then enhances the nectin-nectin interaction, which further enhances the nectin-afadin interaction in a positive feedback manner. Thus, the Necl-5-nectin, nectin-nectin, and nectin-afadin interactions cooperatively increase the clustering of the nectin-afadin complex at the cell-cell contact sites, promoting the formation of the nectin-based cell-cell adhesion.
Highlights
Nectins are Ig-like cell-cell adhesion molecules that compose a family of four members, nectin-1, -2, -3, and -4 [1,2,3]
We used the extracellular region of nectin-1 fused to the Fc portion of human IgG (FcNef-1) because Fc-Nef-1 trans-interacts with nectin-3 when it is added to cells expressing nectin-3 [23]
These results indicate that the trans-interaction of nectin-3 with Fc-Nef-1 enhances the binding of afadin to nectin-3
Summary
Nectins are Ig-like cell-cell adhesion molecules that compose a family of four members, nectin-1, -2, -3, and -4 [1,2,3]. The nectin cell adhesion molecules interact in trans with each other through their extracellular regions and with afadin through their cytoplasmic tails, forming adherens junctions in cooperation with cadherins. The Necl-5-nectin, nectin-nectin, and nectin-afadin interactions cooperatively increase the clustering of the nectin-afadin complex at the cellcell contact sites, promoting the formation of the nectin-based cell-cell adhesion.
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