μ-Protocadherin, a novel developmentally regulated protocadherin with mucin-like domains

Abstract

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 μ-protocadherin, reflecting the hybrid nature of its extracellular region. μ-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. μ-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 μ-protocadherin with β-catenin was noted primarily at the junction of the lateral and basal merebrahe. The cytoplasmic domain contains four prolinerich regions, similar to SH3 binding regions. Thus, it is likely that adhesive interactions mediated by μ-protocadherin induce signaling events that regulate branching morphogenesis.