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

Science. 2010 Jan 22;327(5964):459-63. doi: 10.1126/science.1179802.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning
  • Cell Line
  • Cell Line, Tumor
  • Central Nervous System / cytology
  • Central Nervous System / embryology
  • Embryo, Nonmammalian / metabolism
  • Frizzled Receptors / metabolism
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • LDL-Receptor Related Proteins / metabolism
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Phosphorylation
  • Prorenin Receptor
  • RNA, Small Interfering
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction*
  • 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*
  • beta Catenin / metabolism

Substances

  • Frizzled Receptors
  • Homeodomain Proteins
  • LDL-Receptor Related Proteins
  • LRP6 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Lrp6 protein, mouse
  • Nerve Tissue Proteins
  • RNA, Small Interfering
  • Receptors, Cell Surface
  • Wnt Proteins
  • Wnt3 Protein
  • Xenopus Proteins
  • beta Catenin
  • engrailed 2 protein
  • Vacuolar Proton-Translocating ATPases
  • Prorenin Receptor