title: Sorcin links calcium signaling to vesicle trafficking, regulates Polo-like kinase 1 and is necessary for mitosis.
abstract: Sorcin, a protein overexpressed in many multi-drug resistant cancers, dynamically localizes to distinct subcellular sites in 3T3-L1 fibroblasts during cell-cycle progression. During interphase sorcin is in the nucleus, in the plasma membrane, in endoplasmic reticulum (ER) cisternae, and in ER-derived vesicles localized along the microtubules. These vesicles are positive to RyR, SERCA, calreticulin and Rab10. At the beginning of mitosis, sorcin-containing vesicles associate with the mitotic spindle, and during telophase are concentrated in the cleavage furrow and, subsequently, in the midbody. Sorcin regulates dimensions and calcium load of the ER vesicles by inhibiting RYR and activating SERCA. Analysis of sorcin interactome reveals calcium-dependent interactions with many proteins, including Polo-like kinase 1 (PLK1), Aurora A and Aurora B kinases. Sorcin interacts physically with PLK1, is phosphorylated by PLK1 and induces PLK1 autophosphorylation, thereby regulating kinase activity. Knockdown of sorcin results in major defects in mitosis and cytokinesis, increase in the number of rounded polynucleated cells, blockage of cell progression in G2/M, apoptosis and cell death. Sorcin regulates calcium homeostasis and is necessary for the activation of mitosis and cytokinesis.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC -Universidad Autónoma de Madrid, Departamento Biología Celular e Inmunología, Cantoblanco; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
authors.forename: Vasiliki S
authors.initials: VS
authors.lastname: Lalioti
authors.affiliation: CNR-National Research Council of Italy, Institute of Molecular Biology and Pathology c/o Department of Biochemical Sciences "A. Rossi Fanelli", University "Sapienza" P.le A.Moro 5, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ilari
authors.affiliation: Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Dublin, Ireland.
authors.forename: David J
authors.initials: DJ
authors.lastname: O'Connell
authors.affiliation: Department of Biochemical Sciences "A. Rossi Fanelli", University "Sapienza" P.le A.Moro 5, Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Poser
authors.affiliation: Centro de Biología Molecular Severo Ochoa, CSIC -Universidad Autónoma de Madrid, Departamento Biología Celular e Inmunología, Cantoblanco; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
authors.forename: Ignacio V
authors.initials: IV
authors.lastname: Sandoval
authors.affiliation: CNR-National Research Council of Italy, Institute of Molecular Biology and Pathology c/o Department of Biochemical Sciences "A. Rossi Fanelli", University "Sapienza" P.le A.Moro 5, Rome, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Colotti
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D008938:Mitosis / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D016415:Sequence Alignment; D022161:Transport Vesicles; D000097869:Polo-Like Kinase 1
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C503113:SRI protein, human