μ-Protocadherin, a Novel Developmentally Regulated Protocadherin with Mucin-like Domains*
- From the Departments of ‡Pediatrics and¶Medicine and Physiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032
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 membrane. The cytoplasmic domain contains four proline-rich regions, similar to SH3 binding regions. Thus, it is likely that adhesive interactions mediated by μ-protocadherin induce signaling events that regulate branching morphogenesis.
Footnotes
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↵* This work was funded by National Institutes of Health Grant DK 55388-01, a March of Dimes award, and Spunk Fund, Inc (to M. G.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) .
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↵§ To whom correspondence should be addressed: Dept. of Pediatrics, College of Physicians and Surgeons of Columbia University, 3959 Broadway BHS Rm. 724, New York, NY 10032. Tel.: 212-305-1559; Fax: 212-305-3475; E-mail: mg81@columbia.edu.
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Published, JBC Papers in Press, May 5, 2000, DOI 10.1074/jbc.M000234200
- Abbreviations:
- mAb
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monoclonal antibody
- PCR
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polymerase chain reaction
- NANIII
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neuraminidase III
- ELISA
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enzyme-linked immunosorbent assay
- PAGE
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polyacrylamide gel electrophoresis
- HPLC
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high performance liquid chromatography
- RT
-
reverse transcriptase
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- Received January 12, 2000.
- Revision received May 4, 2000.
- The American Society for Biochemistry and Molecular Biology, Inc.
