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.Základní údaje
Originální název
Tiam1 regulates the Wnt/Dvl/Rac1 signaling pathway and the differentiation of midbrain dopaminergic neurons.
Autoři
ČAJÁNEK, Lukáš (203 Česká republika), Sri Ranjani GANJI (356 Indie, domácí), Catarina HENRIQUES-OLIVIA (752 Švédsko), Spyridon THEOFILOPOULOS (300 Řecko), Peter KONÍK (703 Slovensko), Vítězslav BRYJA (203 Česká republika, garant, domácí) a Ernest ARENAS (724 Španělsko)
Vydání
Molecular and cellular biology, 2013, 0270-7306
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30105 Physiology
Stát vydavatele
Spojené státy
Utajení
není předmětem státního či obchodního tajemství
Impakt faktor
Impact factor: 5.036
Kód RIV
RIV/00216224:14310/13:00066065
Organizační jednotka
Přírodovědecká fakulta
UT WoS
000317184200007
Klíčová slova anglicky
Wnt; Dvl; Rac1; Tiam1
Změněno: 10. 3. 2015 13:52, Mgr. et Mgr. Veronika Oškerová, Ph.D.
Anotace
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.
Návaznosti
| EE2.3.20.0180, projekt VaV |
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| GA204/09/0498, projekt VaV |
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| GD204/09/H058, projekt VaV |
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| MSM0021622430, záměr |
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