Membrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP5

Abstract The highly conserved Wnt signaling pathway regulates cell proliferation and differentiation in vertebrates and invertebrates. Upon binding of a Wnt ligand to a receptor of the Fz family, Disheveled (Dsh/Dvl) transduces the signal during canonical and non-canonical Wnt signaling. The specifi...

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Autores principales:	Prameet Kaur, Vanessa Yuk Man Lam, Anirudh Gautam Mannava, Jahnavi Suresh, Andreas Jenny, Nicholas S. Tolwinski
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f0b54aded1a04e80b4c93f85536b5bf0
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spelling	oai:doaj.org-article:f0b54aded1a04e80b4c93f85536b5bf02021-12-02T15:18:51ZMembrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP510.1038/s41598-017-04414-02045-2322https://doaj.org/article/f0b54aded1a04e80b4c93f85536b5bf02017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04414-0https://doaj.org/toc/2045-2322Abstract The highly conserved Wnt signaling pathway regulates cell proliferation and differentiation in vertebrates and invertebrates. Upon binding of a Wnt ligand to a receptor of the Fz family, Disheveled (Dsh/Dvl) transduces the signal during canonical and non-canonical Wnt signaling. The specific details of how this process occurs have proven difficult to study, especially as Dsh appears to function as a switch between different branches of Wnt signaling. Here we focus on the membrane-proximal events that occur once Dsh is recruited to the membrane. We show that membrane-tethering of the Dsh protein is sufficient to induce canonical Wnt signaling activation even in the absence of the Wnt co-receptor Arrow/LRP5/6. We map the protein domains required for pathway activation in membrane tethered constructs finding that both the DEP and PDZ domains are dispensable for canonical signaling only in membrane-tethered Dsh, but not in untethered/normal Dsh. These data lead to a signal activation model, where Arrow is required to localize Dsh to the membrane during canonical Wnt signaling placing Dsh downstream of Arrow.Prameet KaurVanessa Yuk Man LamAnirudh Gautam MannavaJahnavi SureshAndreas JennyNicholas S. TolwinskiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Prameet Kaur Vanessa Yuk Man Lam Anirudh Gautam Mannava Jahnavi Suresh Andreas Jenny Nicholas S. Tolwinski Membrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP5
description	Abstract The highly conserved Wnt signaling pathway regulates cell proliferation and differentiation in vertebrates and invertebrates. Upon binding of a Wnt ligand to a receptor of the Fz family, Disheveled (Dsh/Dvl) transduces the signal during canonical and non-canonical Wnt signaling. The specific details of how this process occurs have proven difficult to study, especially as Dsh appears to function as a switch between different branches of Wnt signaling. Here we focus on the membrane-proximal events that occur once Dsh is recruited to the membrane. We show that membrane-tethering of the Dsh protein is sufficient to induce canonical Wnt signaling activation even in the absence of the Wnt co-receptor Arrow/LRP5/6. We map the protein domains required for pathway activation in membrane tethered constructs finding that both the DEP and PDZ domains are dispensable for canonical signaling only in membrane-tethered Dsh, but not in untethered/normal Dsh. These data lead to a signal activation model, where Arrow is required to localize Dsh to the membrane during canonical Wnt signaling placing Dsh downstream of Arrow.
format	article
author	Prameet Kaur Vanessa Yuk Man Lam Anirudh Gautam Mannava Jahnavi Suresh Andreas Jenny Nicholas S. Tolwinski
author_facet	Prameet Kaur Vanessa Yuk Man Lam Anirudh Gautam Mannava Jahnavi Suresh Andreas Jenny Nicholas S. Tolwinski
author_sort	Prameet Kaur
title	Membrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP5
title_short	Membrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP5
title_full	Membrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP5
title_fullStr	Membrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP5
title_full_unstemmed	Membrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP5
title_sort	membrane targeting of disheveled can bypass the need for arrow/lrp5
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f0b54aded1a04e80b4c93f85536b5bf0
work_keys_str_mv	AT prameetkaur membranetargetingofdisheveledcanbypasstheneedforarrowlrp5 AT vanessayukmanlam membranetargetingofdisheveledcanbypasstheneedforarrowlrp5 AT anirudhgautammannava membranetargetingofdisheveledcanbypasstheneedforarrowlrp5 AT jahnavisuresh membranetargetingofdisheveledcanbypasstheneedforarrowlrp5 AT andreasjenny membranetargetingofdisheveledcanbypasstheneedforarrowlrp5 AT nicholasstolwinski membranetargetingofdisheveledcanbypasstheneedforarrowlrp5
_version_	1718387483600748544

Membrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP5

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