2026-04-29T12:24:22Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/259102025-12-18T12:59:50Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587
Repisalud
author
Domínguez-Berzosa, Laura
author
Cantarero, Lara
author
Rodríguez-Sanz, María
author
Tort, Gemma
author
Garrido, Elena
author
Troya-Balseca, Johanna
author
Sáez, María
author
Castro-Martínez, Xóchitl Helga
author
Fernandez-Lizarbe, Sara
author
Urquizu, Edurne
author
Calvo, Enrique
author
López, Juan Antonio
author
Palomo, Tomás
author
Palau, Francesc
author
Hoenicka, Janet
funder
Instituto de Salud Carlos III
funder
Centro de Investigación Biomédica en Red - CIBERCV (Enfermedades Cardiovasculares)
funder
Centro de Investigación Biomédica en Red - CIBERSAM (Salud Mental)
funder
Ministerio de Ciencia e Innovación (España)
funder
Fundación ProCNIC
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
2024-12-19T11:41:21Z
2024-12-19T11:41:21Z
2024-10-04
Int J Mol Sci. 2024 Oct 4;25(19):10705.
International Journal of Molecular Sciences
39409035
https://hdl.handle.net/20.500.12105/25910
The IA polymorphism is a marker of both the Ankyrin Repeat and Kinase Domain containing I gene () encoding a RIP-kinase, and the gene for the dopamine receptor D2. Despite a large number of studies of IA in addictions and other psychiatric disorders, there is difficulty in interpreting this genetic phenomenon due to the lack of knowledge about ANKK1 function. In SH-SY5Y neuroblastoma models, we show that ANKK1 interacts with the synapse protein FERM ARH/RhoGEF and Pleckstrin Domain 1 (FARP1), which is a guanine nucleotide exchange factor (GEF) of the RhoGTPases RAC1 and RhoA. ANKK1-FARP1 colocalized in F-ACTIN-rich structures for neuronal maturation and migration, and both proteins activate the Wnt/PCP pathway. ANKK1, but not FARP1, promotes neuritogenesis, and both proteins are involved in neuritic spine outgrowth. Notably, the knockdown of or affects RhoGTPases expression and neural differentiation. Additionally, ANKK1 binds WGEF, another GEF of Wnt/PCP, regulating its interaction with RhoA. During neuronal differentiation, ANKK1-WGEF interaction is downregulated, while ANKK1-FARP1 interaction is increased, suggesting that ANKK1 recruits Wnt/PCP components for bidirectional control of F-ACTIN assembly. Our results suggest a brain structural basis in IA-associated phenotypes.
eng
ANKK1
F-ACTIN
FARP1
TaqIA
Wnt/PCP
addictions
ANKK1 Is a Wnt/PCP Scaffold Protein for Neural F-ACTIN Assembly.
research article
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URL
https://repisalud.isciii.es/bitstreams/e555388a-b7b3-49c8-b82e-f93f1cc404bd/download
File
MD5
0d3543283d34545b268f81971da0eeda
4821143
application/pdf
ANKK1 Is a Wnt_Int J Mol Sci_2024.pdf