title: Coiled-coil domain containing protein 124 is a novel centrosome and midbody protein that interacts with the Ras-guanine nucleotide exchange factor 1B and is involved in cytokinesis.
abstract: Cytokinetic abscission is the cellular process leading to physical separation of two postmitotic sister cells by severing the intercellular bridge. The most noticeable structural component of the intercellular bridge is a transient organelle termed as midbody, localized at a central region marking the site of abscission. Despite its major role in completion of cytokinesis, our understanding of spatiotemporal regulation of midbody assembly is limited. Here, we report the first characterization of coiled-coil domain-containing protein-124 (Ccdc124), a eukaryotic protein conserved from fungi-to-man, which we identified as a novel centrosomal and midbody protein. Knockdown of Ccdc124 in human HeLa cells leads to accumulation of enlarged and multinucleated cells; however, centrosome maturation was not affected. We found that Ccdc124 interacts with the Ras-guanine nucleotide exchange factor 1B (RasGEF1B), establishing a functional link between cytokinesis and activation of localized Rap2 signaling at the midbody. Our data indicate that Ccdc124 is a novel factor operating both for proper progression of late cytokinetic stages in eukaryotes, and for establishment of Rap2 signaling dependent cellular functions proximal to the abscission site.
authors.affiliation: Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, Ankara, Turkey.
authors.forename: Pelin
authors.initials: P
authors.lastname: Telkoparan
authors.forename: Serap
authors.initials: S
authors.lastname: Erkek
authors.forename: Elif
authors.initials: E
authors.lastname: Yaman
authors.forename: Hani
authors.initials: H
authors.lastname: Alotaibi
authors.forename: Defne
authors.initials: D
authors.lastname: Bayık
authors.forename: Uygar H
authors.initials: UH
authors.lastname: Tazebay
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D018385:Centrosome / Q000378:metabolism*; D048749:Cytokinesis / Q000502:physiology*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics; D015388:Organelles / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D021381:Protein Transport; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013692:Telophase / Q000235:genetics; D020668:rap GTP-Binding Proteins / Q000378:metabolism; D020663:ras Guanine Nucleotide Exchange Factors / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D020668:rap GTP-Binding Proteins; D020663:ras Guanine Nucleotide Exchange Factors; C586662:CCDC124 protein, human; C116756:RAP2A protein, human
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