Recombinant Cynomolgus/Rhesus Macaque Nectin-1 Protein, CF

Nectin-1 (designated CD111), also called PRR-1 (poliovirus receptor-related protein 1) or HVEC (herpesvirus entry mediator C), is a widely expressed 110 kDa type I transmembrane glycoprotein important in formation of adherens junctions and synapses. It is a member of the nectin family within the Ig superfamily (1, 2). The Latin word necto means "to connect", indicating the role of nectins in Ca²⁺-independent cell-cell adhesion (2). Nectin-1 forms homodimers in cis, followed by interactions in trans with Nectin-1, -3 or -4 (2). Based on the similarity with human Nectin-1, the 519 amino acid (aa) cynomolgus Nectin-1 may contain a 30 aa signal sequence, a 328 aa extracellular domain (ECD), a 21 aa transmembrane segment (TM), and a 140 aa cytoplasmic region. Nectin ECDs contain three Ig-like domains: an N-terminal V-type that mediates ligand binding, and two C2-type (3,4). The ECD of cynomolgus Nectin-1 shares 98% and 100% aa identity with human and rhesus monkey Nectin-1, respectively. Nectin-1 binds viral glycoprotein D to mediate herpesvirus (but not poxvirus) entry into vaginal mucosa, sensory neurons and fibroblasts (4 - 7). In forming adherens junctions and synapses, nectins 1 and 3 initiate cell-cell interactions, recruiting alpha v beta 3 integrin extracellularly and cadherins intracellularly through afadin and other junctional proteins (2, 8 - 11). These interactions organize the cytoskeleton, strengthen attachment to basement membrane and promote further cell-cell connections. Nectin-1 also recognizes CD96 on NK cells (12). Deficiency of Nectin-1 can result in cleft lip/palate ectodermal dysplasia (13). Nectin-1 downregulation in epithelial cancers, mediated in part by ectodomain shedding, may contribute to invasiveness (14). In colorectal cancer, Nectin-1 expression was found to be associated with a high risk for early disease recurrence (15).