Related Experiment Video

Updated: Jun 13, 2026

Modeling Paracrine Noncanonical Wnt Signaling In Vitro
11:14

Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Published on: December 10, 2021

Ror2/Frizzled complex mediates Wnt5a-induced AP-1 activation by regulating Dishevelled polymerization

Michiru Nishita1, Sumiyo Itsukushima, Akira Nomachi

  • 1Department of Physiology and Cell Biology, Graduate School of Medicine, Kobe University, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. nishita@med.kobe-u.ac.jp

Molecular and Cellular Biology
|May 12, 2010
PubMed

Insights

The Ror2 receptor tyrosine kinase and Frizzled7 form a complex to regulate Wnt5a signaling. This complex controls Dishevelled polymerization, crucial for the Wnt5a/Rac1/AP-1 pathway.

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Receptor Tyrosine Kinases

Background:

  • Ror2 is a receptor tyrosine kinase involved in Wnt5a signaling, mediating JNK pathway activation and canonical Wnt pathway inhibition.
  • The precise mechanism of Ror2 cooperation with other receptors in Wnt5a signaling remains unclear.

Purpose of the Study:

  • To elucidate the role of Ror2 in Wnt5a signaling pathways.
  • To identify cooperating receptor components and downstream effectors in Ror2-mediated Wnt5a signaling.

Main Methods:

  • Investigated Ror2's interaction with Frizzled7 (Fz7) using its extracellular domain.
  • Assessed the impact of Ror2 and Fz7 on Dishevelled (Dvl) polymerization and AP-1 promoter activation.
  • Examined the role of Dvl domains (DIX and DEP) and Rac1 in Wnt5a signaling.

Main Results:

  • Ror2 regulates Wnt5a-induced Dishevelled (Dvl) polymerization independently of its cytoplasmic region.
  • Ror2 associates with Frizzled7 (Fz7) via its extracellular domain to form a receptor complex essential for Dvl regulation and AP-1 activation.
  • Fz7 suppression inhibits Wnt5a-induced Dvl polymerization and AP-1 activation.
  • Both DIX and DEP domains of Dvl are critical for polymerization and AP-1 activation.
  • Polymerized Dvl colocalizes with Rac1, and Rac1 suppression inhibits Wnt5a-induced AP-1 activation.

Conclusions:

  • The Ror2/Fz7 receptor complex is crucial for Wnt5a signaling.
  • This complex regulates Dvl polymerization, a key step in the Wnt5a/Rac1/AP-1 pathway.

More Related Videos

The Power of Simplicity: Sea Urchin Embryos as in Vivo Developmental Models for Studying Complex Cell-to-cell Signaling Network Interactions07:34

The Power of Simplicity: Sea Urchin Embryos as in Vivo Developmental Models for Studying Complex Cell-to-cell Signaling Network Interactions

Published on: February 16, 2017

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
Mechanism of Lamellipodia Formation01:31

Mechanism of Lamellipodia Formation

Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...