The Addiction-Related Protein ANKK1 is Differentially Expressed During the Cell Cycle in Neural Precursors
Por:
España-Serrano L, Guerra Martín-Palanco N, Montero-Pedrazuela A, Pérez-Santamarina E, Vidal R, García-Consuegra I, Valdizán EM, Pazos A, Palomo T, Jiménez-Arriero MÁ, Guadaño-Ferraz A and Hoenicka J
Publicada:
1 may 2017
Ahead of Print:
10 may 2016
Resumen:
TaqIA is a polymorphism associated 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 show significant 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.
Filiaciones:
España-Serrano L:
Laboratory of Neurosciences, Psychiatry Department, Instituto de Investigación Sanitaria del Hospital Universitario 12 de Octubre, Madrid 28041, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Spain
Guerra Martín-Palanco N:
Laboratory of Neurosciences, Psychiatry Department, Instituto de Investigación Sanitaria del Hospital Universitario 12 de Octubre, Madrid 28041, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Spain
Montero-Pedrazuela A:
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC) and Universidad Autónoma de Madrid, Madrid 28029, Spain
Pérez-Santamarina E:
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Spain Centro de Investigación Príncipe Felipe, Valencia 46012, Spain
Vidal R:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Spain Departamento de Fisiología y Farmacología, Universidad de Cantabria, Instituto de Biomedicina y Biotecnología de Cantabria (UC-CSIC-SODERCAN), Santander 39011, Spain
García-Consuegra I:
Laboratory of Neurosciences, Psychiatry Department, Instituto de Investigación Sanitaria del Hospital Universitario 12 de Octubre, Madrid 28041, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Spain
Valdizán EM:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Spain Departamento de Fisiología y Farmacología, Universidad de Cantabria, Instituto de Biomedicina y Biotecnología de Cantabria (UC-CSIC-SODERCAN), Santander 39011, Spain
Pazos A:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Spain Departamento de Fisiología y Farmacología, Universidad de Cantabria, Instituto de Biomedicina y Biotecnología de Cantabria (UC-CSIC-SODERCAN), Santander 39011, Spain
Palomo T:
Laboratory of Neurosciences, Psychiatry Department, Instituto de Investigación Sanitaria del Hospital Universitario 12 de Octubre, Madrid 28041, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Spain
Jiménez-Arriero MÁ:
Laboratory of Neurosciences, Psychiatry Department, Instituto de Investigación Sanitaria del Hospital Universitario 12 de Octubre, Madrid 28041, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Spain
Guadaño-Ferraz A:
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC) and Universidad Autónoma de Madrid, Madrid 28029, Spain
Hoenicka J:
Laboratory of Neurosciences, Psychiatry Department, Instituto de Investigación Sanitaria del Hospital Universitario 12 de Octubre, Madrid 28041, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Spain Centro de Investigación Príncipe Felipe, Valencia 46012, Spain Laboratory of Neurogenetics and Molecular Medicine, Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona 08950, Spain
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