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Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration

Michiru Nishita1, Sa Kan Yoo, Akira Nomachi

  • 1Department of Genome Sciences, Faculty of Medical Sciences, Graduate School of Medicine, Kobe University, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.

The Journal of Cell Biology
|November 15, 2006
PubMed

Insights

Receptor tyrosine kinase Ror2 is crucial for Wnt5a-induced cell migration by promoting filopodia formation. This process requires Ror2

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Signaling

Background:

  • Receptor tyrosine kinase Ror2 is involved in developmental processes.
  • Ror2 mediates Wnt5a-induced noncanonical Wnt signaling via Wnt-JNK pathway activation and beta-catenin-TCF pathway inhibition.
  • The role of Ror2 in noncanonical Wnt signaling-driven cell migration remains unclear.

Purpose of the Study:

  • To investigate the function of Ror2 in noncanonical Wnt signaling, specifically in cell migration.
  • To elucidate the molecular mechanisms by which Ror2 regulates Wnt5a-induced cell migration.

Main Methods:

  • Utilized genetically diverse and manipulated cultured cell lines.
  • Investigated the roles of Ror2's extracellular cysteine-rich domain (CRD) and cytoplasmic proline-rich domain (PRD).
  • Examined Ror2-mediated filopodia formation and its dependence on actin reorganization and filamin A.

Main Results:

  • Ror2 is essential for Wnt5a-induced, but not Wnt3a-induced, cell migration.
  • Ror2-mediated cell migration necessitates its CRD (Wnt5a binding site) and PRD.
  • Ror2 induces filopodia formation via actin reorganization, requiring filamin A binding to its PRD.
  • Inhibition of Ror2 or filamin A suppresses filopodia formation and consequently Wnt5a-induced cell migration.

Conclusions:

  • Ror2 plays a critical role in Wnt5a-induced cell migration.
  • Ror2-mediated filopodia formation, dependent on filamin A, is essential for Wnt5a-induced cell migration.
  • The CRD and PRD domains of Ror2 are vital for its function in cell migration.

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