Functional characterization of WNT7A signaling in PC12 cells: Interaction with a FZD5-LRP6 receptor complex and modulation by Dickkopf proteins

Andrea Caricasole, Teresa Ferraro, Luisa Iacovelli, Eliana Barletta, Alessandra Caruso, Daniela Melchiorri, Georg C. Terstappen, Ferdinando Nicoletti

Research output: Contribution to journalArticlepeer-review

Abstract

WNT factors represent key mediators of many processes in animal development and homeostasis and act through a receptor complex comprised of members of the Frizzled and low density lipoprotein-related receptors (LRP). In mammals, 19 genes encoding Wingless and Int-related factor (WNTs), 10 encoding Frizzled, and 2 encoding LRP proteins have been identified, but little is known of the identities of individual Frizzled-LRP combinations mediating the effects of specific WNT factors. Additionally, several secreted modulators of WNT signaling have been identified, including at least three members of the Dickkopf family. WNT7A is a WNT family member expressed in the vertebrate central nervous system capable of modulating aspects of neuronal plasticity. Gene knock-out models in the mouse have revealed that WNT7A plays a role in cerebellar maturation, although its function in the development of distal limb structures and of the reproductive tract have been more intensely studied. To identify a receptor complex for this WNT family member, we have analyzed the response of the rat pheochromocytoma cell line PC12 to WNT7A. We find that PC12 cells are capable of responding to WNT7A as measured by increased β-catenin stability and activation of a T-cell factor-based luciferase reporter construct and that these cells express three members of the Frizzled family (Frizzled-2, -5, and -7) and LRP6. Our functional analysis indicates that WNT7A can specifically act via a Frizzled-5·LRP6 receptor complex in PC12 cells and that this activity can be antagonized by Dickkopf-1 and Dickkopf-3.

Original languageEnglish
Pages (from-to)37024-37031
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number39
DOIs
Publication statusPublished - Sep 26 2003

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Functional characterization of WNT7A signaling in PC12 cells: Interaction with a FZD5-LRP6 receptor complex and modulation by Dickkopf proteins'. Together they form a unique fingerprint.

Cite this