Recombinant Human Cadherin-4/R-Cadherin Fc Chimera, CF

The cadherin superfamily is a large family of membrane-associated glycoproteins that engage in both homo- and heterotypic, calcium-dependent, cell-cell adhesion events. The superfamily can be divided into at least four subfamilies based on its member’s extracellular (EC) regions and cytoplasmic domains (1, 2). These include classical cadherins, desmosomal cadherins, protocadherins, and cadherin-like molecules that contain a variable number of EC and transmembrane (TM) domains (1). Cadherin-4, also known as R-cadherin, is a classical cadherin of 120 - 140 kDa (3, 4). Human Cadherin-4 is synthesized as a 916 amino acid (aa) type I transmembrane glycoprotein that contains a 20 aa signal peptide, a 149 aa prosequence, a 565 aa extracellular region (EC), a 22 aa transmembrane segment, and a 160 aa cytoplasmic domain (5, 6). There are five EC cadherin domains that are approximately 110 aa in length. This pattern is consistent with classical cadherin family molecules that are modular in their extracellular region and mediate calcium-dependent cell-cell adhesion through their Ca⁺⁺-binding repeats (2). One potential Cadherin-4 splice variant involves the preprosegment and shows 32 aa substitution for theN-terminal 124 amino of the full-length precursor (7). The extracellular region of human Cadherin-4 is 96% aa identical to mouse Cadherin-4 extracellular region (3). Cadherin-4 is expressed in vascular smooth muscle (8), pancreatic beta -cells (9), thyroid follicular cells (10), bone marrow Lin^- HSCs (11), sensory neurons of the dorsal root ganglia (12), and, possibly, astrocytes and endothelium of the retina (13). As a classic cadherin, Cadherin-4 will form both homodimers and heterodimers with N-cadherin (4, 14). These complexes translate into adhesion multimers in cis- and trans-configurations. Such structures serve to both unite adjacent cells, and provide guidance for migrating cells/processes (13). Additionally, R-cadherin is associated with cell quiescence, as a loss of cell Cadherin-4 expression is correlated with cell proliferation (8). Finally, R-cadherin is reported to bind to KLRG1 (killer cell lectin-like receptor G1). This inactivates NK cell cytotoxicity, and provides protection for R-cadherin expressing cells (15).