title: Differential expression and localization of Ankrd2 isoforms in human skeletal and cardiac muscles.
abstract: Four human Ankrd2 transcripts, reported in the Ensembl database, code for distinct protein isoforms (360, 333, 327 and 300 aa), and so far, their existence, specific expression and localization patterns have not been studied in detail. Ankrd2 is preferentially expressed in the slow fibers of skeletal muscle. It is found in both the nuclei and the cytoplasm of skeletal muscle cells, and its localization is prone to change during differentiation and upon stress. Ankrd2 has also been detected in the heart, in ventricular cardiomyocytes and in the intercalated disks (ICDs). The main objective of this study was to distinguish between the Ankrd2 isoforms and to determine the contribution of each one to the general profile of Ankrd2 expression in striated muscles. We demonstrated that the known expression and localization pattern of Ankrd2 in striated muscle can be attributed to the isoform of 333 aa which is dominant in both tissues, while the designated cardiac and canonical isoform of 360 aa was less expressed in both tissues. The 360 aa isoform has a distinct nuclear localization in human skeletal muscle, as well as in primary myoblasts and myotubes. In contrast to the isoform of 333 aa, it was not preferentially expressed in slow fibers and not localized to the ICDs of human cardiomyocytes. Regulation of the expression of both isoforms is achieved at the transcriptional level. Our results set the stage for investigation of the specific functions and interactions of the Ankrd2 isoforms in healthy and diseased human striated muscles.
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, PO Box 23, Belgrade, 11010, Serbia.
authors.forename: Jovana
authors.initials: J
authors.lastname: Jasnic-Savovic
authors.affiliation: Department of Neurology, Friedrich Baur Institute, Ludwig Maximilians University, Ziemssenstr. 1a, 80336, Munich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Krause
authors.affiliation: Institute of Forensic Medicine, School of Medicine, University of Belgrade, Deligradska 31a, Belgrade, 11000, Serbia.
authors.forename: Slobodan
authors.initials: S
authors.lastname: Savic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, PO Box 23, Belgrade, 11010, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Kojic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, PO Box 23, Belgrade, 11010, Serbia.
authors.forename: Vlado
authors.initials: V
authors.lastname: Kovcic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, PO Box 23, Belgrade, 11010, Serbia.
authors.forename: Srdjan
authors.initials: S
authors.lastname: Boskovic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, PO Box 23, Belgrade, 11010, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Nestorovic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, PO Box 23, Belgrade, 11010, Serbia.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Rakicevic
authors.affiliation: Department of Neurology, Friedrich Baur Institute, Ludwig Maximilians University, Ziemssenstr. 1a, 80336, Munich, Germany.
authors.forename: Olivia
authors.initials: O
authors.lastname: Schreiber-Katz
authors.affiliation: Department of Neurology, Friedrich Baur Institute, Ludwig Maximilians University, Ziemssenstr. 1a, 80336, Munich, Germany.
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Vogel
authors.affiliation: Department of Neurology, Friedrich Baur Institute, Ludwig Maximilians University, Ziemssenstr. 1a, 80336, Munich, Germany.
authors.forename: Benedikt G
authors.initials: BG
authors.lastname: Schoser
authors.affiliation: Department of Neurology, Friedrich Baur Institute, Ludwig Maximilians University, Ziemssenstr. 1a, 80336, Munich, Germany.
authors.forename: Maggie C
authors.initials: MC
authors.lastname: Walter
authors.affiliation: CRIBI, University of Padova, Via Ugo Bassi 58b, 35121, Padua, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Valle
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, PO Box 23, Belgrade, 11010, Serbia.
authors.forename: Dragica
authors.initials: D
authors.lastname: Radojkovic
authors.affiliation: CRIBI, University of Padova, Via Ugo Bassi 58b, 35121, Padua, Italy.
authors.forename: Georgine
authors.initials: G
authors.lastname: Faulkner
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, PO Box 23, Belgrade, 11010, Serbia. snezanakojic@imgge.bg.ac.rs.
authors.forename: Snezana
authors.identifier: http://orcid.org/0000-0001-5090-1278
authors.initials: S
authors.lastname: Kojic
mesh_terms: D000595:Amino Acid Sequence; D002478:Cells, Cultured; D006801:Humans; D009124:Muscle Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020033:Protein Isoforms / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: C432364:ANKRD2 protein, human; D009124:Muscle Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012097:Repressor Proteins
keywords: Ankrd2; Heart; Human; Isoforms; Skeletal muscle