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oai:repisalud.isciii.es:20.500.12105/184652024-11-28T15:47:04Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc Baeza, Victor author Cifuentes, Manuel author Martínez, Fernando author Ramírez, Eder author Nualart, Francisco author Ferrada, Luciano author Oviedo, María José author De Lima, Isabelle author Troncoso, Ninoschka author Saldivia, Natalia author Salazar, Katterine author 2021-09-17 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. http://hdl.handle.net/10668/4196 http://hdl.handle.net/20.500.12105/18465 34535732 10.1038/s41598-021-97948-3 2045-2322 Scientific Reports Caspase-3 Adherens junctions Gliosis Cadherins Ependymoma Adenovirus Cells Caspasa 3 Uniones adherentes Cadherinas Ependimoma Adenoviridae Células IIIG9 inhibition in adult ependymal cells changes adherens junctions structure and induces cellular detachment