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	Johan Sternemalm, Stefan Geimer, Kari-Anne M Frikstad, Kay O Schink, Trond Stokke, Sebastian Patzke
Journal	PloS one (PLoS One) Vol. 10 Issue 8 Pg. e0134789 ( 2015) ISSN: 1932-6203 [Electronic] United States
PMID	26241740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	CSPP1 protein, human CSPP1 protein, mouse Cell Cycle Proteins DSP protein, human Desmoplakins Microtubule-Associated Proteins Neoplasm Proteins RNA, Small Interfering
Topics	Adenocarcinoma (pathology) Animals Cell Culture Techniques Cell Cycle Proteins (antagonists & inhibitors, genetics, physiology) Cell Line, Tumor Cell Polarity Colonic Neoplasms (pathology) Cytoskeleton (ultrastructure) Desmoplakins (physiology) Desmosomes (chemistry) Dogs Epithelial Cells (metabolism, ultrastructure) Humans Intercellular Junctions (physiology, ultrastructure) Madin Darby Canine Kidney Cells Mice Microtubule-Associated Proteins (analysis, antagonists & inhibitors, genetics, physiology) Microtubules (physiology) Morphogenesis Neoplasm Proteins (antagonists & inhibitors, genetics, physiology) RNA Interference RNA, Small Interfering (genetics) Spheroids, Cellular Trachea (chemistry, ultrastructure)

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