Corpus ID: 16885214

WNT/FZD Signaling: An Odyssey from Molecular Pharmacology to Brain (Patho)Physiology

  title={WNT/FZD Signaling: An Odyssey from Molecular Pharmacology to Brain (Patho)Physiology},
  author={J. P. Dijksterhuis},
The 19 members of the lipoglycoprotein family of WNTs interact with the highly conserved cysteine-rich domain (CRD) of ten members of the Frizzled (FZD1-10) family. The seven transmembrane-spanning surface receptors are listed as G protein-coupled receptors and are known to interact with heterotrimeric G proteins as well as the scaffolding protein disheveled. Upon ligand binding, activation of β-catenin-dependent and/or –independent pathways are induced. The WNT/Frizzled signaling pathway is… Expand


The Frizzled family of unconventional G-protein-coupled receptors.
The current state of knowledge on FZDs and FZD signal transduction is outlined and aspects of debate and future directions are pinpointed. Expand
Heterotrimeric G protein-dependent WNT-5A signaling to ERK1/2 mediates distinct aspects of microglia proinflammatory transformation
WNT-5A emerges as an important means of astrocyte-microglia communication and is suggested as a new player in neuroinflammatory conditions, such as neurodegenerative disease, hypoxia, stroke, injury and infection. Expand
International Union of Basic and Clinical Pharmacology. LXXX. The Class Frizzled Receptors
  • G. Schulte
  • Medicine, Biology
  • Pharmacological Reviews
  • 2010
This review focuses on the molecular aspects of WNT/FZD and HH/SMO signaling discussing receptor structure, mechanisms of signal transduction, accessory proteins, receptor dynamics, and the possibility of targeting these signaling pathways pharmacologically. Expand
Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling
It is shown that the rat protein Frizzled-2 causes an increase in the release of intracellular calcium which is enhanced by Xwnt-5a, a member of the Wnt family, and this indicates that some Wnt proteins work through specific FriZZled homologues to stimulate the phosphatidylinositol signalling pathway via heterotrimeric G-protein subunits. Expand
Assessment of Frizzled 6 membrane mobility by FRAP supports G protein coupling and reveals WNT-Frizzled selectivity.
A novel way to assess WNT-FZD interaction by live cell imaging is introduced allowing further mapping of WNT and FZD interactions and challenging previous experimental limitations. Expand
Structural Basis of Wnt Recognition by Frizzled
The 3.25 angstrom structure of Xenopus Wnt8 (XWnt8) in complex with mouse Frizzled-8 (Fz8) cysteine-rich domain (CRD) reveals an unusual two-domain Wnt structure, resembling a “hand” with “thumb” and “index” fingers extended to grasp the Fz8-CRD at two distinct binding sites. Expand
Ryk is essential for Wnt-5a-dependent invasiveness in human glioma.
Findings suggest that Fz-2 and Ryk could be therapeutic or pharmacological target molecules for the control of Wnt-5a-dependent invasion of human glioma in the near future and that Ryk might have a novel patho-physiological function in adult cancer invasion. Expand
Dishevelled: The hub of Wnt signaling.
The current understanding of Dvl functions in Wnt signal transduction and its biological functions in mouse development are summarized, and the molecular mechanisms of its actions are discussed. Expand
Trimeric G Protein-Dependent Frizzled Signaling in Drosophila
Roles for the Galpha(o) subunit (Go) in mediating the two distinct pathways transduced by Fz receptors in Drosophila: the Wnt and planar polarity pathways are shown. Expand
WNT-5A stimulates the GDP/GTP exchange at pertussis toxin-sensitive heterotrimeric G proteins.
Molecular proof is provided for the first time molecular proof that WNT-5A stimulation results in the activation of heterotrimeric G(i2/3) proteins in mammalian cells with physiological protein stochiometry. Expand