Mu-Protocadherin, a Novel Developmentally Regulated Protocadherin with Mucin-like Domains

Branching morphogenesis is a central event during the development of kidneys, lungs, and other organs. We previously generated a monoclonal antibody, 3D2-E9, that inhibited branching morphogenesis and caused widespread apoptosis. We now report the purification of its antigen and cloning of its full-length cDNA. Its cDNA encodes an integral membrane protein that contains four cadherin-like ectodomains and a thrice tandemly repeated region enriched in threonine, serine, and proline, similar to those of mucins. We thus term this protein mu-protocadherin, reflecting the hybrid nature of its extracellular region. mu-Protocadherin is expressed in two forms that are developmentally regulated, with the shorter isoform lacking the mucin-like repeats. Expression of the long isoform in heterologous cells results in adhesion of the expressing cells, suggesting that it is a new cell adhesion molecule. mu-Protocadherin contains both N and O glycosylations. It is expressed at lateral and basal surfaces of epithelia during kidney and lung development and is located in coated pits. Colocalization of mu-protocadherin with beta-catenin was noted primarily at the junction of the lateral and basal membrane. The cytoplasmic domain contains four proline-rich regions, similar to SH3 binding regions. Thus, it is likely that adhesive interactions mediated by mu-protocadherin induce signaling events that regulate branching morphogenesis.