title: The Addiction-Related Protein ANKK1 is Differentially Expressed During the Cell Cycle in Neural Precursors.
abstract: 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.
authors.affiliation: 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.
authors.forename: Laura
authors.initials: L
authors.lastname: España-Serrano
authors.affiliation: 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.
authors.forename: Noelia
authors.initials: N
authors.lastname: Guerra Martín-Palanco
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC) and Universidad Autónoma de Madrid, Madrid 28029, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Montero-Pedrazuela
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Spain.|Centro de Investigación Príncipe Felipe, Valencia 46012, Spain.
authors.forename: Estela
authors.initials: E
authors.lastname: Pérez-Santamarina
authors.affiliation: 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.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Vidal
authors.affiliation: 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.
authors.forename: Inés
authors.initials: I
authors.lastname: García-Consuegra
authors.affiliation: 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.
authors.forename: Elsa María
authors.initials: EM
authors.lastname: Valdizán
authors.affiliation: 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.
authors.forename: Angel
authors.initials: A
authors.lastname: Pazos
authors.affiliation: 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.
authors.forename: Tomás
authors.initials: T
authors.lastname: Palomo
authors.affiliation: 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.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Jiménez-Arriero
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC) and Universidad Autónoma de Madrid, Madrid 28029, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Guadaño-Ferraz
authors.affiliation: 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.
authors.forename: Janet
authors.initials: J
authors.lastname: Hoenicka
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D004622:Embryo, Mammalian; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D005865:Gestational Age; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007223:Infant; D051379:Mice; D008875:Middle Aged; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; C498585:TUBB3 protein, human; D014404:Tubulin; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: ANKK1; DRD2; TaqIA; addictions; cell cycle; neurogenesis