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Science 327 (5964): 459-463

Copyright © 2010 by the American Association for the Advancement of Science

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

Cristina-Maria Cruciat,1,* Bisei Ohkawara,1,* Sergio P. Acebron,1 Emil Karaulanov,1 Carmen Reinhard,1 Dierk Ingelfinger,2 Michael Boutros,2 Christof Niehrs1,{dagger}

Abstract: Wnt/β-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/β-catenin signaling.

1 Division of Molecular Embryology, DKFZ-ZMBH Alliance, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
2 Division of Signaling and Functional Genomics, Deutsches Krebsforschungszentrum and University of Heidelberg, Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: niehrs{at}dkfz-heidelberg.de


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