IIIG9 inhibition in adult ependymal cells changes adherens junctions structure and induces cellular detachment

Abstract Ependymal cells have multiple apical cilia that line the ventricular surfaces and the central canal of spinal cord. In cancer, the loss of ependymal cell polarity promotes the formation of different types of tumors, such as supratentorial anaplastic ependymomas, which are highly aggressive...

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Autores principales:	Victor Baeza, Manuel Cifuentes, Fernando Martínez, Eder Ramírez, Francisco Nualart, Luciano Ferrada, María José Oviedo, Isabelle De Lima, Ninoschka Troncoso, Natalia Saldivia, Katterine Salazar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ae82d70191ff4511854dc48d57c6fbe3
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spelling	oai:doaj.org-article:ae82d70191ff4511854dc48d57c6fbe32021-12-02T17:23:46ZIIIG9 inhibition in adult ependymal cells changes adherens junctions structure and induces cellular detachment10.1038/s41598-021-97948-32045-2322https://doaj.org/article/ae82d70191ff4511854dc48d57c6fbe32021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97948-3https://doaj.org/toc/2045-2322Abstract Ependymal cells have multiple apical cilia that line the ventricular surfaces and the central canal of spinal cord. In cancer, the loss of ependymal cell polarity promotes the formation of different types of tumors, such as supratentorial anaplastic ependymomas, which are highly aggressive in children. IIIG9 (PPP1R32) is a protein restricted to adult ependymal cells located in cilia and in the apical cytoplasm and has unknown function. In this work, we studied the expression and localization of IIIG9 in the adherens junctions (cadherin/β-catenin-positive junctions) of adult brain ependymal cells using confocal and transmission electron microscopy. Through in vivo loss-of-function studies, ependymal denudation (single-dose injection experiments of inhibitory adenovirus) was observed, inducing the formation of ependymal cells with a “balloon-like” morphology. These cells had reduced cadherin expression (and/or delocalization) and cleavage of the cell death marker caspase-3, with “cilia rigidity” morphology (probably vibrational beating activity) and ventriculomegaly occurring prior to these events. Finally, after performing continuous infusions of adenovirus for 14 days, we observed total cell denudation and reactive parenchymal astrogliosis. Our data confirmed that IIIG9 is essential for the maintenance of adherens junctions of polarized ependymal cells. Eventually, altered levels of this protein in ependymal cell differentiation may increase ventricular pathologies, such as hydrocephalus or neoplastic transformation.Victor BaezaManuel CifuentesFernando MartínezEder RamírezFrancisco NualartLuciano FerradaMaría José OviedoIsabelle De LimaNinoschka TroncosoNatalia SaldiviaKatterine SalazarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Victor Baeza Manuel Cifuentes Fernando Martínez Eder Ramírez Francisco Nualart Luciano Ferrada María José Oviedo Isabelle De Lima Ninoschka Troncoso Natalia Saldivia Katterine Salazar IIIG9 inhibition in adult ependymal cells changes adherens junctions structure and induces cellular detachment
description	Abstract Ependymal cells have multiple apical cilia that line the ventricular surfaces and the central canal of spinal cord. In cancer, the loss of ependymal cell polarity promotes the formation of different types of tumors, such as supratentorial anaplastic ependymomas, which are highly aggressive in children. IIIG9 (PPP1R32) is a protein restricted to adult ependymal cells located in cilia and in the apical cytoplasm and has unknown function. In this work, we studied the expression and localization of IIIG9 in the adherens junctions (cadherin/β-catenin-positive junctions) of adult brain ependymal cells using confocal and transmission electron microscopy. Through in vivo loss-of-function studies, ependymal denudation (single-dose injection experiments of inhibitory adenovirus) was observed, inducing the formation of ependymal cells with a “balloon-like” morphology. These cells had reduced cadherin expression (and/or delocalization) and cleavage of the cell death marker caspase-3, with “cilia rigidity” morphology (probably vibrational beating activity) and ventriculomegaly occurring prior to these events. Finally, after performing continuous infusions of adenovirus for 14 days, we observed total cell denudation and reactive parenchymal astrogliosis. Our data confirmed that IIIG9 is essential for the maintenance of adherens junctions of polarized ependymal cells. Eventually, altered levels of this protein in ependymal cell differentiation may increase ventricular pathologies, such as hydrocephalus or neoplastic transformation.
format	article
author	Victor Baeza Manuel Cifuentes Fernando Martínez Eder Ramírez Francisco Nualart Luciano Ferrada María José Oviedo Isabelle De Lima Ninoschka Troncoso Natalia Saldivia Katterine Salazar
author_facet	Victor Baeza Manuel Cifuentes Fernando Martínez Eder Ramírez Francisco Nualart Luciano Ferrada María José Oviedo Isabelle De Lima Ninoschka Troncoso Natalia Saldivia Katterine Salazar
author_sort	Victor Baeza
title	IIIG9 inhibition in adult ependymal cells changes adherens junctions structure and induces cellular detachment
title_short	IIIG9 inhibition in adult ependymal cells changes adherens junctions structure and induces cellular detachment
title_full	IIIG9 inhibition in adult ependymal cells changes adherens junctions structure and induces cellular detachment
title_fullStr	IIIG9 inhibition in adult ependymal cells changes adherens junctions structure and induces cellular detachment
title_full_unstemmed	IIIG9 inhibition in adult ependymal cells changes adherens junctions structure and induces cellular detachment
title_sort	iiig9 inhibition in adult ependymal cells changes adherens junctions structure and induces cellular detachment
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ae82d70191ff4511854dc48d57c6fbe3
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IIIG9 inhibition in adult ependymal cells changes adherens junctions structure and induces cellular detachment

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