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Reorganization of actin cytoskeleton by FRIED, a Frizzled‐8 associated protein tyrosine phosphatase
Author(s) -
Itoh Keiji,
Lisovsky Mikhail,
Hikasa Hiroki,
Sokol Sergei Y.
Publication year - 2005
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.20526
Subject(s) - frizzled , biology , microbiology and biotechnology , pdz domain , xenopus , wnt signaling pathway , actin cytoskeleton , cytoskeleton , protein tyrosine phosphatase , ferm domain , signal transduction , membrane protein , biochemistry , integral membrane protein , cell , gene , membrane
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 ( Fr izzled i nteraction and e ctoderm d efects) 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.