Identification and expression analysis of the human mu-protocadherin gene in fetal and adult kidneys.
We recently cloned mu-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 mu-protocadherin in L929 cells resulted in cellular aggregation, confirming its role in intercellular adhesion. We now identify the human mu-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 mu-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. Mu-protocadherin is apically expressed along the brush border of the proximal convoluted tubule of the adult kidney. Transfection of truncated forms of mu-protocadherin into polarized Madin-Darby canine kidney cells reveals that the NH(2) terminus is essential for targeting to the apical surface. These results suggest that although human mu-protocadherin may mediate a homotypic adhesive interaction, it may have additional functions in terminally differentiated epithelia.
Goldberg
Michael
M
Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. mg81@columbia.edu
Wei
Michelle
M
Tycko
Benjamin
B
Falikovich
Inna
I
Warburton
Dorothy
D
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D002448:Cell Adhesion; D002460:Cell Line; D016384:Consensus Sequence; D004285:Dogs; D004848:Epithelium / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D015870:Gene Expression; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007668:Kidney / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009077:Mucins / Q000737:chemistry; D051381:Rats; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D014162:Transfection
C413024:CDHR5 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; C504544:Cdhr5 protein, rat; D009077:Mucins