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The addiction-related protein ANKK1 is differentially expressed during the cell cycle in neural precursors

Abstract: TaqIA is a polymorphismassociated with addictions and dopamine-related traits. It is located in the ankyrin repeat and kinase domain containing 1 gene (ANKK1) nearby the gene for the dopamine D2 receptor (D2R). Since ANKK1 function is unknown, TaqIA-associated traits have been explained only by differences in D2R. Here we report ANKK1 studies in mouse and human brain using quantitative real-time PCR, Western blot, immunohistochemistry, and flow cytometry. ANKK1 mRNA and protein isoforms vary along neurodevelopment in the human and mouse brain. In mouse adult brain ANKK1 is located in astrocytes, nuclei of postmitotic neurons and neural precursors from neurogenic niches. In both embryos and adults, nuclei of neural precursors showsignificant variation of ANKK1 intensity.We demonstrate a correlation between ANKK1 and the cell cycle. Cell synchronization experiments showed a significant increment of ANKK1-kinase in mitotic cells while ANKK1-kinase overexpression affects G1 and M phase that were found to be modulated by ANKK1 alleles and apomorphine treatment. Furthermore, during embryonic neurogenesis ANKK1 was expressed in slow-dividing neuroblasts and rapidly dividing precursors which are mitotic cells. These results suggest a role of ANKK1 during the cell cycle in neural precursors thus providing biological support to brain structure involvement in the TaqIA-associated phenotypes.

 Fuente: Cerebral Cortex, 2017, 27(5), 2809-2819

 Editorial: Oxford University Press

 Año de publicación: 2017

 Nº de páginas: 11

 Tipo de publicación: Artículo de Revista

 DOI: 10.1093/cercor/bhw129

 ISSN: 1047-3211,1460-2199

 Proyecto español: SAF2014-54919-R ; SAF2011-25020

 Url de la publicación: https://doi.org/10.1093/cercor/bhw129

Authorship

ESPAÑA SERRANO, LAURA

GUERRA MARTÍN PALANCO, NOELIA

MONTERO PEDRAZUELA, ANA

PÉREZ SANTAMARINA, ESTELA

REBECA VIDAL CASADO

GARCÍA CONSUEGRA, INÉS

ELSA MARIA VALDIZAN RUIZ

PALOMO, TOMÁS

JIMÉNEZ ARRIERO, MIGUEL ÁNGEL

GUADAÑO FERRAZ, ANA

HOENICKA, JANET