mu-protocadherin, a novel developmentally regulated protocadherin with mucin-like domains

Branching morphogenesis is a central event during the development of kidney s, lungs, and other organs. We previously generated a monoclonal antibody, 3D2-E9, that inhibited branching morphogenesis and caused widespread apopto sis, We now report the purification of its antigen and cloning of its full- length cDNA. Its cDNA. encodes an integral membrane protein that contains f our cadherin-like ectodomains and a thrice tandemly repeated region enriche d in threonine, serine, and proline, similar to those of mucins, We thus te rm this protein mu-protocadherin, reflecting the hybrid nature of its extra cellular region, mu-Protocadherin is expressed in two forms that are develo pmentally regulated, with the shorter isoform lacking the mucin-like repeat s. Expression of the long isoform in heterologous cells results in adhesion of the expressing cells, suggesting that it is a new cell adhesion molecul e. mu-Protocadherin contains both N and O glycosylations. It is expressed a t lateral and basal surfaces of epithelia during kidney and lung developmen t and is located in coated pits. Colocalization of mu-protocadherin with be ta-catenin was noted primarily at the junction of the lateral and basal mem brane. The cytoplasmic domain contains four proline-rich regions, similar t o SH3 binding regions, Thus, it is likely that adhesive interactions mediat ed by mu-protocadherin induce signaling events that regulate branching morp hogenesis.