Keiji Itoh and Mikhail Lisovksy made equal contributions to this work.
Reorganization of actin cytoskeleton by FRIED, a Frizzled-8 associated protein tyrosine phosphatase
Article first published online: 5 AUG 2005
Copyright © 2005 Wiley-Liss, Inc.
Volume 234, Issue 1, pages 90–101, September 2005
How to Cite
Itoh, K., Lisovsky, M., Hikasa, H. and Sokol, S. Y. (2005), Reorganization of actin cytoskeleton by FRIED, a Frizzled-8 associated protein tyrosine phosphatase. Dev. Dyn., 234: 90–101. doi: 10.1002/dvdy.20526
- Issue published online: 16 AUG 2005
- Article first published online: 5 AUG 2005
- Manuscript Accepted: 10 JUN 2005
- Manuscript Revised: 5 MAY 2005
- Manuscript Received: 3 FEB 2005
- March of Dimes Birth Defect Foundation
- National Institutes of Health
Frizzled receptors transduce signals from the extracellular Wnt ligands through multiple signaling pathways that affect cytoskeletal organization and regulate gene expression. Direct intracellular mediators of Frizzled signaling are largely unknown. We identified FRIED (Frizzled interaction and ectoderm defects) by its association with the C-terminal PDZ-binding motif of Xenopus Frizzled 8. FRIED contains an N-terminal KIND domain, a FERM domain, six PDZ domains, and a tyrosine phosphatase domain, being similar in structure to the protein tyrosine phosphatase PTP-BAS/PTP-BL. We report that FRIED proteins with the FERM domain localize to the apical cortex and can inhibit Wnt8-mediated, but not β-catenin-mediated, secondary axis induction in Xenopus embryos, suggesting a specific interaction with Wnt signaling. A FRIED construct containing the FERM domain induced reorganization of pigment granules and cortical actin in Xenopus ectoderm. Wnt5a suppressed the depigmentation of ectoderm triggered by FRIED, demonstrating that Wnt5a and FRIED functionally interact to regulate the cytoskeletal organization. Our data are consistent with the possibility that FRIED functions by modulating Rac1 activity. We propose that FRIED is an adaptor protein that serves as a molecular link between Wnt signaling and actin cytoskeleton. Developmental Dynamics 234:90–101, 2005. © 2005 Wiley-Liss, Inc.