Detailed Information on Publication Record
2013
Tiam1 regulates the Wnt/Dvl/Rac1 signaling pathway and the differentiation of midbrain dopaminergic neurons.
ČAJÁNEK, Lukáš, Sri Ranjani GANJI, Catarina HENRIQUES-OLIVIA, Spyridon THEOFILOPOULOS, Peter KONÍK et. al.Basic information
Original name
Tiam1 regulates the Wnt/Dvl/Rac1 signaling pathway and the differentiation of midbrain dopaminergic neurons.
Authors
ČAJÁNEK, Lukáš (203 Czech Republic), Sri Ranjani GANJI (356 India, belonging to the institution), Catarina HENRIQUES-OLIVIA (752 Sweden), Spyridon THEOFILOPOULOS (300 Greece), Peter KONÍK (703 Slovakia), Vítězslav BRYJA (203 Czech Republic, guarantor, belonging to the institution) and Ernest ARENAS (724 Spain)
Edition
Molecular and cellular biology, 2013, 0270-7306
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
30105 Physiology
Country of publisher
United States of America
Confidentiality degree
není předmětem státního či obchodního tajemství
Impact factor
Impact factor: 5.036
RIV identification code
RIV/00216224:14310/13:00066065
Organization unit
Faculty of Science
UT WoS
000317184200007
Keywords in English
Wnt; Dvl; Rac1; Tiam1
Změněno: 10/3/2015 13:52, Mgr. et Mgr. Veronika Oškerová, Ph.D.
Abstract
V originále
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. Finally, using ventral midbrain neurosphere cultures, we demonstrate that the generation of DA neurons in culture is impaired after Tiam1 knockdown, indicating that Tiam1 is required for midbrain DA differentiation. In summary, our data identify Tiam1 as a novel regulator of DA neuron development and as a Dvl-associated and Rac1-specific GEF acting in the Wnt/Dvl/Rac1 pathway.
Links
| EE2.3.20.0180, research and development project |
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| GA204/09/0498, research and development project |
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| GD204/09/H058, research and development project |
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| MSM0021622430, plan (intention) |
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