About: Tiam1 regulates the Wnt/Dvl/Rac1 signaling pathway and the differentiation of midbrain dopaminergic neurons.

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About: Tiam1 regulates the Wnt/Dvl/Rac1 signaling pathway and the differentiation of midbrain dopaminergic neurons. Goto Sponge NotDistinct Permalink

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	Understanding the mechanisms that drive the differentiation of dopaminergic (DA) neurons is crucial for successful development of novel therapies for Parkinson's disease, in which DA neurons progressively degenerate. However, the mechanisms underlying the differentiation-promoting effects of Wnt5a on DA precursors are poorly understood. Here, we present the molecular and functional characterization of a signaling pathway downstream of Wnt5a, the Wnt/Dvl/Rac1 pathway. First, we characterize the interaction between Rac1 and Dvl and identify the N-terminal part of Dvl3 as necessary for Rac1 binding. Next, we show that Tiam1, a Rac1 guanosine exchange factor (GEF), is expressed in the ventral midbrain, interacts with Dvl, facilitates Dvl-Rac1 interaction, and is required for Dvl- or Wnt5a-induced activation of Rac1. Moreover, we show that Wnt5a promotes whereas casein kinase 1 (CK1), a negative regulator of the Wnt/Dvl/Rac1 pathway, abolishes the interactions between Dvl and Tiam1. Understanding the mechanisms that drive the differentiation of dopaminergic (DA) neurons is crucial for successful development of novel therapies for Parkinson's disease, in which DA neurons progressively degenerate. However, the mechanisms underlying the differentiation-promoting effects of Wnt5a on DA precursors are poorly understood. Here, we present the molecular and functional characterization of a signaling pathway downstream of Wnt5a, the Wnt/Dvl/Rac1 pathway. First, we characterize the interaction between Rac1 and Dvl and identify the N-terminal part of Dvl3 as necessary for Rac1 binding. Next, we show that Tiam1, a Rac1 guanosine exchange factor (GEF), is expressed in the ventral midbrain, interacts with Dvl, facilitates Dvl-Rac1 interaction, and is required for Dvl- or Wnt5a-induced activation of Rac1. Moreover, we show that Wnt5a promotes whereas casein kinase 1 (CK1), a negative regulator of the Wnt/Dvl/Rac1 pathway, abolishes the interactions between Dvl and Tiam1. (en)
Title	Tiam1 regulates the Wnt/Dvl/Rac1 signaling pathway and the differentiation of midbrain dopaminergic neurons. Tiam1 regulates the Wnt/Dvl/Rac1 signaling pathway and the differentiation of midbrain dopaminergic neurons. (en)
skos:prefLabel	Tiam1 regulates the Wnt/Dvl/Rac1 signaling pathway and the differentiation of midbrain dopaminergic neurons. Tiam1 regulates the Wnt/Dvl/Rac1 signaling pathway and the differentiation of midbrain dopaminergic neurons. (en)
skos:notation	RIV/00216224:14310/13:00066065!RIV14-MSM-14310___
http://linked.open...avai/riv/aktivita	I P S Z
http://linked.open...avai/riv/aktivity	I, P(EE2.3.20.0180), P(GA204/09/0498), P(GD204/09/H058), S, Z(MSM0021622430)
http://linked.open...iv/cisloPeriodika	1
http://linked.open...vai/riv/dodaniDat	2014
http://linked.open...aciTvurceVysledku	Bryja, Vítězslav Ganji, Sri Ranjani
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Masarykova univerzita / Přírodovědecká fakulta
http://linked.open...dnocenehoVysledku	111056
http://linked.open...ai/riv/idVysledku	RIV/00216224:14310/13:00066065
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	Wnt; Dvl; Rac1; Tiam1 (en)
http://linked.open.../riv/klicoveSlovo	Dvl Rac1 Tiam1 Wnt
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[0519413E9E66]
http://linked.open...i/riv/nazevZdroje	Molecular and cellular biology
http://linked.open...in/vavai/riv/obor	ED
http://linked.open...ichTvurcuVysledku	2 (xsd:int)
http://linked.open...cetTvurcuVysledku	7 (xsd:int)
http://linked.open...vavai/riv/projekt	Cooperation between Masaryk University and Karolinska Institutet, Stockholm in the field of biomedicine Intercellular signalling in development and disease Dynamics of proteins interacting with Dishevelled and their importance for Wnt signalling
http://linked.open...UplatneniVysledku	2013
http://linked.open...v/svazekPeriodika	33
http://linked.open...iv/tvurceVysledku	Bryja, Vítězslav Koník, Peter Ganji, Sri Ranjani Arenas, Ernest Čajánek, Lukáš Henriques-Olivia, Catarina Theofilopoulos, Spyridon
http://linked.open...ain/vavai/riv/wos	000317184200007
http://linked.open...n/vavai/riv/zamer	Functional and molecular characteristics of cancer and normal stem cells - identification of targets for novel therapeutics and therapeutic strategies
issn	0270-7306
number of pages	12 (xsd:int)
http://bibframe.org/vocab/doi	10.1128/MCB.00745-12
http://localhost/t...ganizacniJednotka	14310

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