mu-Protocadherin, a novel developmentally regulated protocadherin with mucin-like domains.
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 mu-protocadherin, reflecting the hybrid nature of its extracellular region. mu-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. mu-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 mu-protocadherin with beta-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 mu-protocadherin induce signaling events that regulate branching morphogenesis.
Goldberg
M
M
Departments of Pediatrics and Medicine and Physiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA. mg81@columbia.edu
Peshkovsky
C
C
Shifteh
A
A
Al-Awqati
Q
Q
D000595:Amino Acid Sequence; D000818:Animals; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000737:chemistry* / Q000235:genetics* / Q000302:isolation & purification; D002449:Cell Aggregation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental; D006031:Glycosylation; D007668:Kidney / Q000196:embryology / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009077:Mucins / Q000737:chemistry*; D009928:Organ Specificity; D011487:Protein Conformation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D020449:Repetitive Sequences, Amino Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014162:Transfection
D000070585:Cadherin Related Proteins; D015820:Cadherins; C504544:Cdhr5 protein, rat; D009077:Mucins; D012333:RNA, Messenger; D011994:Recombinant Proteins