title: CSPP-L Associates with the Desmosome of Polarized Epithelial Cells and Is Required for Normal Spheroid Formation.
abstract: Deleterious mutations of the Centrosome/Spindle Pole associated Protein 1 gene, CSPP1, are causative for Joubert-syndrome and Joubert-related developmental disorders. These disorders are defined by a characteristic mal-development of the brain, but frequently involve renal and hepatic cyst formation. CSPP-L, the large protein isoform of CSPP1 localizes to microtubule ends of the mitotic mid-spindle and the ciliary axoneme, and is required for ciliogenesis. We here report the microtubule independent but Desmoplakin dependent localization of CSPP-L to Desmosomes in apical-basal polarized epithelial cells. Importantly, siRNA conferred depletion of CSPP-L or Desmoplakin promoted multi-lumen spheroid formation in 3D-cultures of non-ciliated human colon carcinoma Caco-2 cells. Multi-lumen spheroids of CSPP1 siRNA transfectants showed disrupted apical cell junction localization of the cytoskeleton organizing RhoGEF ECT2. Our results hence identify a novel, non-ciliary role for CSPP-L in epithelial morphogenesis.
authors.affiliation: Department of Radiation Biology, Division of Cancer Medicine, Surgery and Transplantation, Institute for Cancer Research, Oslo University Hospitals-Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Johan
authors.initials: J
authors.lastname: Sternemalm
authors.affiliation: Cell Biology/Electron Microscopy, University of Bayreuth, Bayreuth, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Geimer
authors.affiliation: Department of Radiation Biology, Division of Cancer Medicine, Surgery and Transplantation, Institute for Cancer Research, Oslo University Hospitals-Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Kari-Anne M
authors.initials: KA
authors.lastname: Frikstad
authors.affiliation: Department of Molecular Cell Biology, Division of Cancer Medicine, Surgery and Transplantation, Institute for Cancer Research, Oslo University Hospitals-Norwegian Radium Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Kay O
authors.initials: KO
authors.lastname: Schink
authors.affiliation: Department of Radiation Biology, Division of Cancer Medicine, Surgery and Transplantation, Institute for Cancer Research, Oslo University Hospitals-Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Trond
authors.initials: T
authors.lastname: Stokke
authors.affiliation: Department of Radiation Biology, Division of Cancer Medicine, Surgery and Transplantation, Institute for Cancer Research, Oslo University Hospitals-Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Patzke
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D018929:Cell Culture Techniques; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D016764:Cell Polarity; D003110:Colonic Neoplasms / Q000473:pathology; D003599:Cytoskeleton / Q000648:ultrastructure; D051180:Desmoplakins / Q000502:physiology; D003896:Desmosomes / Q000737:chemistry*; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure*; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology / Q000648:ultrastructure; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008870:Microtubules / Q000502:physiology; D009024:Morphogenesis; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D018874:Spheroids, Cellular; D014132:Trachea / Q000737:chemistry / Q000648:ultrastructure
chemical_list: C514207:CSPP1 protein, human; C000607565:CSPP1 protein, mouse; D018797:Cell Cycle Proteins; C495294:DSP protein, human; D051180:Desmoplakins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering