title: Localization of α-Dystrobrevin in Cajal Bodies and Nucleoli: A New Role for α-Dystrobrevin in the Structure/Stability of the Nucleolus.
abstract: α-Dystrobrevin (α-DB) is a cytoplasmic component of the dystrophin-associated complex involved in cell signaling; however, its recently revealed nuclear localization implies a role for this protein in the nucleus. Consistent with this, we demonstrated, in a previous work that α-DB1 isoform associates with the nuclear lamin to maintain nuclei morphology. In this study, we show the distribution of the α-DB2 isoform in different subnuclear compartments of N1E115 neuronal cells, including nucleoli and Cajal bodies, where it colocalizes with B23/nucleophosmin and Nopp140 and with coilin, respectively. Recovery in a pure nucleoli fraction undoubtedly confirms the presence of α-DB2 in the nucleolus. α-DB2 redistributes in a similar fashion to that of fibrillarin and Nopp140 upon actinomycin-mediated disruption of nucleoli and to that of coilin after disorganization of Cajal bodies through ultraviolet-irradiation, with relocalization of the proteins to the corresponding reassembled structures after cessation of the insults, which implies α-DB2 in the plasticity of these nuclear bodies. That localization of α-DB2 in the nucleolus is physiologically relevant is demonstrated by the fact that downregulation of α-DB2 resulted in both altered nucleoli structure and decreased levels of B23/nucleophosmin, fibrillarin, and Nopp140. Since α-DB2 interacts with B23/nucleophosmin and overexpression of the latter protein favors nucleolar accumulation of α-DB2, it appears that targeting of α-DB2 to the nucleolus is dependent on B23/nucleophosmin. In conclusion, we show for the first time localization of α-DB2 in nucleoli and Cajal bodies and provide evidence that α-DB2 is involved in the structure of nucleoli and might modulate nucleolar functions.
authors.affiliation: Departamento de Gen, é, tica y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV- IPN), Mexico City, Mexico.
authors.forename: Jose Anselmo
authors.initials: JA
authors.lastname: Hernández-Ibarra
authors.affiliation: Departamento de Gen, é, tica y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV- IPN), Mexico City, Mexico.
authors.forename: Marco Samuel
authors.initials: MS
authors.lastname: Laredo-Cisneros
authors.affiliation: Departamento de Gen, é, tica y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV- IPN), Mexico City, Mexico.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Mondragón-González
authors.affiliation: Departamento de Ciencias de la Vida, Carrera de Ingeniería en Biotecnología, Universidad de las Fuerzas Armadas-ESPE, Sangolquí, Ecuador.
authors.forename: Natalie
authors.initials: N
authors.lastname: Santamaría-Guayasamín
authors.affiliation: Departamento de Gen, é, tica y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV- IPN), Mexico City, Mexico.
authors.forename: Bulmaro
authors.initials: B
authors.lastname: Cisneros
mesh_terms: D002466:Cell Nucleolus / Q000378:metabolism* / Q000648:ultrastructure; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D020541:Coiled Bodies / Q000378:metabolism* / Q000648:ultrastructure; D049029:Dystrophin-Associated Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D000090243:Nucleophosmin
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C490915:DTNA protein, human; D049029:Dystrophin-Associated Proteins; C000716967:NPM1 protein, human; D009479:Neuropeptides; D009687:Nuclear Proteins; C047458:fibrillarin; D000090243:Nucleophosmin
keywords: B23/NUCLEOPHOSMIN; CAJAL BODIES; COILIN; FIBRILLARIN; N1E115 NEURONAL CELLS; NUCLEAR BODIES; NUCLEOLUS; α-DYSTROBREVIN