The receptor tyrosine kinase Ror2 plays important roles in developmental morphogenesis. It has recently been shown that Ror2 mediates Wnt5a-induced noncanonical Wnt signaling by activating the Wnt–JNK pathway and inhibiting the β-catenin–TCF pathway. However, the function of Ror2 in noncanonical Wnt signaling leading to cell migration is largely unknown. We show, using genetically different or manipulated cultured cells, that Ror2 is critical for Wnt5a-induced, but not Wnt3a-induced, cell migration. Ror2-mediated cell migration requires the extracellular cysteine-rich domain (CRD), which is the binding site for Wnt5a, and the cytoplasmic proline-rich domain (PRD) of Ror2. Furthermore, Ror2 can mediate filopodia formation via actin reorganization, irrespective of Wnt5a, and this Ror2-mediated filopodia formation requires the actin-binding protein filamin A, which associates with the PRD of Ror2. Intriguingly, disruption of filopodia formation by suppressing the expression of either Ror2 or filamin A inhibits Wnt5a-induced cell migration, indicating that Ror2-mediated filopodia formation is essential for Wnt5a-induced cell migration.
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20 November 2006
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November 13 2006
Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration
Michiru Nishita,
Michiru Nishita
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
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Sa Kan Yoo,
Sa Kan Yoo
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
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Akira Nomachi,
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
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Shuichi Kani,
Shuichi Kani
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
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Nagako Sougawa,
Nagako Sougawa
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
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Yasutaka Ohta,
Yasutaka Ohta
2Hematology Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115
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Shinji Takada,
Shinji Takada
3Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences,
4Department of Molecular Biomechanics, Graduate University for Advanced Studies (SOKENDAI), 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8787, Japan
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Akira Kikuchi,
Akira Kikuchi
5Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
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Yasuhiro Minami
Yasuhiro Minami
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
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Michiru Nishita
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
Sa Kan Yoo
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
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
Shuichi Kani
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
Nagako Sougawa
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
Yasutaka Ohta
2Hematology Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115
Shinji Takada
3Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences,
4Department of Molecular Biomechanics, Graduate University for Advanced Studies (SOKENDAI), 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8787, Japan
Akira Kikuchi
5Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
Yasuhiro Minami
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
Correspondence to Yasuhiro Minami: [email protected]
Abbreviations used in this paper: CE, convergent extension; CM, conditioned medium; CRD, cysteine-rich domain; HEK, human embryonic kidney; MEF, mouse embryonic fibroblast; PRD, proline-rich domain.
Received:
July 24 2006
Accepted:
October 10 2006
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2006
J Cell Biol (2006) 175 (4): 555–562.
Article history
Received:
July 24 2006
Accepted:
October 10 2006
Citation
Michiru Nishita, Sa Kan Yoo, Akira Nomachi, Shuichi Kani, Nagako Sougawa, Yasutaka Ohta, Shinji Takada, Akira Kikuchi, Yasuhiro Minami; Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration . J Cell Biol 20 November 2006; 175 (4): 555–562. doi: https://doi.org/10.1083/jcb.200607127
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