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Article: Wnt-induced Vangl2 Phosphorylation Is Dose-Dependently Required for Planar Cell Polarity in Mammalian Development

TitleWnt-induced Vangl2 Phosphorylation Is Dose-Dependently Required for Planar Cell Polarity in Mammalian Development
Authors
Issue Date2017
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/cr/marketing/index.html
Citation
Cell Research, 2017 How to Cite?
AbstractPlanar cell polarity (PCP) is an evolutionarily conserved essential mechanism that provides directional information to control and coordinate polarized cellular and tissue behavior during embryonic development. Disruption of PCP leads to severe morphological defects in vertebrates and its dysregulation results in a variety of human diseases such as neural tube defects and skeletal dysplasia. PCP is governed by a set of highly conserved core proteins that are asymmetrically localized at the cell surface throughout the polarized tissues. The uniform directionality of PCP is established by global cues, such as Wg/Wnt signaling gradients that break the original symmetrical localization of core PCP proteins including Vang/Vangl and Fz/Fzd. However, the exact mechanism remains elusive. In this study, we found that Vangl2 phosphorylation, which was previously identified to be induced by Wnt5a signaling, is required for Vangl2 functions in mammalian PCP in multiple tissues. The in vivo activities of Vangl2 are determined by its phosphorylation level. Phospho-mutant Vangl2 exhibits dominant negative effects, whereas Vangl2 with reduced phosphorylation is hypomorphic. We show that Vangl2 phosphorylation is essential for its uniform polarization pattern. Moreover, serine/threonine kinases CK1ε and CK1δ are redundantly required for Wnt5a-induced Vangl2 phosphorylation. Dvl family members are also required for Wnt5a-induced Vangl2 phosphorylation by enhancing the interaction of CK1 and Vangl2. These findings demonstrate that induction of Vangl protein phosphorylation plays an essential role in transducing Wnt5a signaling to establish PCP in mammalian development, suggesting a phosphorylation-regulated “Vangl activity gradient” model in addition to well-documented “Fz activity gradient” model in Wnt/PCP signaling.
Persistent Identifierhttp://hdl.handle.net/10722/244678
ISSN
2015 Impact Factor: 14.812
2015 SCImago Journal Rankings: 4.805

 

DC FieldValueLanguage
dc.contributor.authorGao, B-
dc.date.accessioned2017-09-18T01:57:03Z-
dc.date.available2017-09-18T01:57:03Z-
dc.date.issued2017-
dc.identifier.citationCell Research, 2017-
dc.identifier.issn1001-0602-
dc.identifier.urihttp://hdl.handle.net/10722/244678-
dc.description.abstractPlanar cell polarity (PCP) is an evolutionarily conserved essential mechanism that provides directional information to control and coordinate polarized cellular and tissue behavior during embryonic development. Disruption of PCP leads to severe morphological defects in vertebrates and its dysregulation results in a variety of human diseases such as neural tube defects and skeletal dysplasia. PCP is governed by a set of highly conserved core proteins that are asymmetrically localized at the cell surface throughout the polarized tissues. The uniform directionality of PCP is established by global cues, such as Wg/Wnt signaling gradients that break the original symmetrical localization of core PCP proteins including Vang/Vangl and Fz/Fzd. However, the exact mechanism remains elusive. In this study, we found that Vangl2 phosphorylation, which was previously identified to be induced by Wnt5a signaling, is required for Vangl2 functions in mammalian PCP in multiple tissues. The in vivo activities of Vangl2 are determined by its phosphorylation level. Phospho-mutant Vangl2 exhibits dominant negative effects, whereas Vangl2 with reduced phosphorylation is hypomorphic. We show that Vangl2 phosphorylation is essential for its uniform polarization pattern. Moreover, serine/threonine kinases CK1ε and CK1δ are redundantly required for Wnt5a-induced Vangl2 phosphorylation. Dvl family members are also required for Wnt5a-induced Vangl2 phosphorylation by enhancing the interaction of CK1 and Vangl2. These findings demonstrate that induction of Vangl protein phosphorylation plays an essential role in transducing Wnt5a signaling to establish PCP in mammalian development, suggesting a phosphorylation-regulated “Vangl activity gradient” model in addition to well-documented “Fz activity gradient” model in Wnt/PCP signaling.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/cr/marketing/index.html-
dc.relation.ispartofCell Research-
dc.titleWnt-induced Vangl2 Phosphorylation Is Dose-Dependently Required for Planar Cell Polarity in Mammalian Development-
dc.typeArticle-
dc.identifier.emailGao, B: gaobo@hku.hk-
dc.identifier.authorityGao, B=rp02012-
dc.identifier.doi10.1038/cr.2017.127-
dc.identifier.hkuros278186-
dc.publisher.placeUnited Kingdom-

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