Tiam1 Regulates the Wnt/Dvl/Rac1 Signaling Pathway and the Differentiation of Midbrain Dopaminergic Neurons

0392710 - BFÚ 2014 RIV US eng J - Článek v odborném periodiku
Čajánek, L. - Ganji, R.S. - Henriques-Oliveira, C. - Theofilopoulos, S. - Koník, P. - Bryja, Vítězslav - Arenas, E.
Tiam1 Regulates the Wnt/Dvl/Rac1 Signaling Pathway and the Differentiation of Midbrain Dopaminergic Neurons.
Molecular and Cellular Biology. Roč. 33, č. 1 (2013), s. 59-70. ISSN 0270-7306. E-ISSN 1098-5549
Grant CEP: GA ČR(CZ) GD204/09/H058
Grant ostatní: GA ČR(CZ) GA204/09/0498
Institucionální podpora: RVO:68081707
Klíčová slova: RHO-GTPASES * CELL POLARITY * DISHEVELLED PHOSPHORYLATION
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 5.036, rok: 2013

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.
Trvalý link: http://hdl.handle.net/11104/0221511