Identification and expression analysis of the human μ-protocadherin gene in fetal and adult kidneys

Abstract

We recently cloned μ-protocadherin, a developmentally regulated cell adhesion molecule that contains an extracellular region with four cadherin-like ectodomains and a triply repeating mucin domain in its longer isoform. Expression of μ-protocadherin in L929 cells resulted in cellular aggregation, confirming its role in intercellular adhesion. We now identify the human μ-protocadherin ortholog and study its distribution in vivo and its targeting in polarized epithelia. Basic Local Alignment Search Tool searches and fluorescent in situ hybridization analysis on the basis of human-mouse synteny reveal that μ-protocadherin maps to 11p15.5, matching a previously identified gene called MUCDHL. At least three different splicing isoforms exist for MUCDHL that vary in expression in the fetal kidney. μ-Protocadherin is apically expressed along the brush border of the proximal convoluted tubule of the adult kidney. Transfection of truncated forms of μ-protocadherin into polarized Madin-Darby canine kidney cells reveals that the NH2terminus is essential for targeting to the apical surface. These results suggest that although human μ-protocadherin may mediate a homotypic adhesive interaction, it may have additional functions in terminally differentiated epithelia.