Requirement of prorenin receptor and vacuolar H+-ATPase-mediated acidification for Wnt signaling.
Wnt/beta-catenin signaling is important in stem cell biology, embryonic development, and disease, including cancer. However, the mechanism of Wnt signal transmission, notably how the receptors are activated, remains incompletely understood. We found that the prorenin receptor (PRR) is a component of the Wnt receptor complex. PRR functions in a renin-independent manner as an adaptor between Wnt receptors and the vacuolar H+-adenosine triphosphatase (V-ATPase) complex. Moreover, PRR and V-ATPase were required to mediate Wnt signaling during antero-posterior patterning of Xenopus early central nervous system development. The results reveal an unsuspected role for the prorenin receptor, V-ATPase activity, and acidification during Wnt/beta-catenin signaling.
Cruciat
Cristina-Maria
CM
Division of Molecular Embryology, DKFZ-ZMBH Alliance, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Ohkawara
Bisei
B
Acebron
Sergio P
SP
Karaulanov
Emil
E
Reinhard
Carmen
C
Ingelfinger
Dierk
D
Boutros
Michael
M
Niehrs
Christof
C
D000818:Animals; D019521:Body Patterning; D002460:Cell Line; D045744:Cell Line, Tumor; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology; D004625:Embryo, Nonmammalian / Q000378:metabolism; D051157:Frizzled Receptors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D026502:LDL-Receptor Related Proteins / Q000378:metabolism; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D060508:Wnt3 Protein; D014981:Xenopus / Q000196:embryology / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism; D000093342:Prorenin Receptor; D000099266:Engrailed 2 Protein
D051157:Frizzled Receptors; D018398:Homeodomain Proteins; D026502:LDL-Receptor Related Proteins; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D025262:Vacuolar Proton-Translocating ATPases; D051153:Wnt Proteins; D060508:Wnt3 Protein; D029867:Xenopus Proteins; D051176:beta Catenin; D000093342:Prorenin Receptor; D000099266:Engrailed 2 Protein; C555475:LRP6 protein, human; C555476:Lrp6 protein, mouse