Requirement of Prorenin Receptor and Vacuolar H⁺ -ATPase-Mediated Acidification for Wnt Signaling

• Published in: Science (American Association for the Advancement of Science) Vol. 327; no. 5964; pp. 459 - 463
• Main Authors: Cruciat, Cristina-Maria, Ohkawara, Bisei, Acebron, Sergio P., Karaulanov, Emil, Reinhard, Carmen, Ingelfinger, Dierk, Boutros, Michael, Niehrs, Christof
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 22.01.2010; The American Association for the Advancement of Science
• Subjects: Acidification; Animals; beta Catenin - metabolism; Biochemistry; Biological and medical sciences; Blastomeres; Body Patterning; Cell Line; Cell Line, Tumor; Cell physiology; Cellular biology; Central Nervous System - cytology; Central Nervous System - embryology; Embryo, Nonmammalian - metabolism; Embryos; Frizzled Receptors - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Genes; HEK293 cells; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; Hydrogen-Ion Concentration; LDL-Receptor Related Proteins - metabolism; Low Density Lipoprotein Receptor-Related Protein-6; Messenger RNA; Mice; Molecular and cellular biology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurons; Phosphorylation; Proteins; Receptors; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; RNA, Small Interfering; Signal Transduction; Small interfering RNA; Vacuolar Proton-Translocating ATPases - antagonists & inhibitors; Vacuolar Proton-Translocating ATPases - metabolism; Wnt Proteins - metabolism; Wnt3 Protein; Xenopus - embryology; Xenopus - metabolism; Xenopus Proteins - genetics; Xenopus Proteins - metabolism; Wnt/β-catenin signaling pathway; Enzyme; Xenopus laevis; Adenosinetriphosphatase; Amphibia; Acidification; Nervous system; Salientia; Vertebrata; Enzymatic activity; β Catenin; Prorenin; Development; Hydrolases; Signal transmission; Mechanism of action; Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1179802

Wnt/ß-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 ͺ -adenosine triphosphatase (V-ATPase) complex. Moreover, PRR and V-ATPase were required to mediate Wnt signaling during antero-posterior patterning oí Xenopus early central nervous system development. The results reveal an unsuspected role for the prorenin receptor, V-ATPase activity, and acidification during Wnt/ß-catenin signaling.