CADM1 is a key receptor mediating human mast cell adhesion to human lung fibroblasts and airway smooth muscle cells.
Authors: Moiseeva, Elena P, Roach, Katy M, Leyland, Mark L, Bradding, Peter
PLoS ONE, 2013;8(4):e61579.
Species: Human
Sample Type: Cell Lysates
Application: WB

Nectins are a small family of Ca⁺⁺-independent immunoglobulin (Ig)-like cell adhesion molecules (CAMs) that organize intercellular junctions (1-4). The Nectin family has at least four members (Nectin-1‑4), all of which show alternate splicing, a transmembrane (TM) region (except for Nectin-1 gamma ), and three extracellular Ig-domains. Nectins are highly homologous to the human receptor for poliovirus, and as such, have been alternatively-named poliovirus receptor-related proteins. They do not, however, appear to bind poliovirus (1). Nectin-3 (also named PRR3, CD113, and PVRL3) is an 83 kDa, type I TM glycoprotein. Its precursor is 549 amino acids (aa) in length. It contains an extended signal sequence of 57 aa, an extracellular domain (ECD) of 347 aa, a transmembrane segment of 21 aa (aa 405-425), and a cytoplasmic region of 124 amino acids. The ECD shows three Ig-like domains; one N-terminal V-type and two membrane-proximal C2-type. The cytoplasmic region shows a Glu-Trp-Tyr-Val motif that binds afadin (3, 5, 6). The ECD of human Nectin-3 is 94% aa identical to mouse Nectin-3 ECD (5, 6). Nectin-3 has a diverse expression pattern. It has been found in junctions between small intestinal columnar epithelial cells (6), pigmented and nonpigmented epithelium in the ciliary body (7), spermatids and Sertoli cells in the seminiferous tubules (8), and on spinal cord motor neurons and axons, plus Schwann cells of the peripheral nervous system (9). As with mouse, human Nectin-3 has three potential isoforms. It does not appear that they are strict orthologs. In addition to the full length isoform, a second human isoform has a 31 aa substitution for the first 54 aa of the signal sequence, followed by a deletion of aa 291-549 (10). The third human isoform shows a 10 aa substitution for aa 357-549 (11). Nectin-3 is proposed to promote cell adhesion by initiating cell-to-cell adhesion, allowing for subsequent JAM and cadherin-based intercellular junction formation. It does so by first forming same cell (cis-) heterodimers with alpha _vbeta₃ and PDGF R (an anti-apoptotic interaction) (2, 4). This results in actin reorganization and recruitment of adherens and occludins adhesion molecules. Subsequent Nectin-3 activity adds strength to the junction through trans-interactions with a variety of molecules, including Nectin-3 itself, as well as Nectins-1 and 2 plus Necl-1, 2 and 5 (3, 4).

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10. GenBank Accession # BAC11414.
11. SwissProt # Q9NQS3.