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

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...

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Autores principales: Nishita, Michiru, Yoo, Sa Kan, Nomachi, Akira, Kani, Shuichi, Sougawa, Nagako, Ohta, Yasutaka, Takada, Shinji, Kikuchi, Akira, Minami, Yasuhiro
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064592/
https://www.ncbi.nlm.nih.gov/pubmed/17101698
http://dx.doi.org/10.1083/jcb.200607127
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author Nishita, Michiru
Yoo, Sa Kan
Nomachi, Akira
Kani, Shuichi
Sougawa, Nagako
Ohta, Yasutaka
Takada, Shinji
Kikuchi, Akira
Minami, Yasuhiro
author_facet Nishita, Michiru
Yoo, Sa Kan
Nomachi, Akira
Kani, Shuichi
Sougawa, Nagako
Ohta, Yasutaka
Takada, Shinji
Kikuchi, Akira
Minami, Yasuhiro
author_sort Nishita, Michiru
collection PubMed
description 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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spelling pubmed-20645922007-11-29 Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration Nishita, Michiru Yoo, Sa Kan Nomachi, Akira Kani, Shuichi Sougawa, Nagako Ohta, Yasutaka Takada, Shinji Kikuchi, Akira Minami, Yasuhiro J Cell Biol Research Articles 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. The Rockefeller University Press 2006-11-20 /pmc/articles/PMC2064592/ /pubmed/17101698 http://dx.doi.org/10.1083/jcb.200607127 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Nishita, Michiru
Yoo, Sa Kan
Nomachi, Akira
Kani, Shuichi
Sougawa, Nagako
Ohta, Yasutaka
Takada, Shinji
Kikuchi, Akira
Minami, Yasuhiro
Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration
title Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration
title_full Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration
title_fullStr Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration
title_full_unstemmed Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration
title_short Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration
title_sort filopodia formation mediated by receptor tyrosine kinase ror2 is required for wnt5a-induced cell migration
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064592/
https://www.ncbi.nlm.nih.gov/pubmed/17101698
http://dx.doi.org/10.1083/jcb.200607127
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