CSPP-L Associates with the Desmosome of Polarized Epithelial Cells and Is Required for Normal Spheroid Formation

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...

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Autores principales: Sternemalm, Johan, Geimer, Stefan, Frikstad, Kari-Anne M., Schink, Kay O., Stokke, Trond, Patzke, Sebastian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524657/
https://www.ncbi.nlm.nih.gov/pubmed/26241740
http://dx.doi.org/10.1371/journal.pone.0134789
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author Sternemalm, Johan
Geimer, Stefan
Frikstad, Kari-Anne M.
Schink, Kay O.
Stokke, Trond
Patzke, Sebastian
author_facet Sternemalm, Johan
Geimer, Stefan
Frikstad, Kari-Anne M.
Schink, Kay O.
Stokke, Trond
Patzke, Sebastian
author_sort Sternemalm, Johan
collection PubMed
description 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.
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spelling pubmed-45246572015-08-06 CSPP-L Associates with the Desmosome of Polarized Epithelial Cells and Is Required for Normal Spheroid Formation Sternemalm, Johan Geimer, Stefan Frikstad, Kari-Anne M. Schink, Kay O. Stokke, Trond Patzke, Sebastian PLoS One Research Article 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. Public Library of Science 2015-08-04 /pmc/articles/PMC4524657/ /pubmed/26241740 http://dx.doi.org/10.1371/journal.pone.0134789 Text en © 2015 Sternemalm et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sternemalm, Johan
Geimer, Stefan
Frikstad, Kari-Anne M.
Schink, Kay O.
Stokke, Trond
Patzke, Sebastian
CSPP-L Associates with the Desmosome of Polarized Epithelial Cells and Is Required for Normal Spheroid Formation
title CSPP-L Associates with the Desmosome of Polarized Epithelial Cells and Is Required for Normal Spheroid Formation
title_full CSPP-L Associates with the Desmosome of Polarized Epithelial Cells and Is Required for Normal Spheroid Formation
title_fullStr CSPP-L Associates with the Desmosome of Polarized Epithelial Cells and Is Required for Normal Spheroid Formation
title_full_unstemmed CSPP-L Associates with the Desmosome of Polarized Epithelial Cells and Is Required for Normal Spheroid Formation
title_short CSPP-L Associates with the Desmosome of Polarized Epithelial Cells and Is Required for Normal Spheroid Formation
title_sort cspp-l associates with the desmosome of polarized epithelial cells and is required for normal spheroid formation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524657/
https://www.ncbi.nlm.nih.gov/pubmed/26241740
http://dx.doi.org/10.1371/journal.pone.0134789
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