Requirement of prorenin receptor and vacuolar H+-ATPase-mediated acidification for Wnt signaling.

Cristina-Maria Cruciat, Bisei Ohkawara, Sergio P Acebron, Emil Karaulanov, Carmen Reinhard, Dierk Ingelfinger, Michael Boutros, Christof Niehrs

Division of Molecular Embryology, DKFZ-ZMBH Alliance, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.

Science (New York, N.Y.) 2010 Jan 22

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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.

Citation

Cristina-Maria Cruciat, Bisei Ohkawara, Sergio P Acebron, Emil Karaulanov, Carmen Reinhard, Dierk Ingelfinger, Michael Boutros, Christof Niehrs. Requirement of prorenin receptor and vacuolar H+-ATPase-mediated acidification for Wnt signaling. Science (New York, N.Y.). 2010 Jan 22;327(5964):459-63