Baeza, VictorCifuentes, ManuelMartínez, FernandoRamírez, EderNualart, FranciscoFerrada, LucianoOviedo, María JoséDe Lima, IsabelleTroncoso, NinoschkaSaldivia, NataliaSalazar, Katterine2022-09-302022-09-302021-09-17Baeza V, Cifuentes M, Martínez F, Ramírez E, Nualart F, Ferrada L, et al. IIIG9 inhibition in adult ependymal cells changes adherens junctions structure and induces cellular detachment. Sci Rep. 2021 Sep 17;11(1):18537http://hdl.handle.net/10668/4196Ependymal 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Caspase-3Adherens junctionsGliosisCadherinsEpendymomaAdenovirusCellsCaspasa 3Uniones adherentesCadherinasEpendimomaAdenoviridaeCélulasMedical Subject Headings::Anatomy::Cells::Cellular Structures::Cell Membrane::Cell Membrane Structures::Intercellular Junctions::Adherens JunctionsMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell AdhesionMedical Subject Headings::Anatomy::Cells::Cells, CulturedMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Cerebral Ventricles::EpendymaMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nerve Tissue ProteinsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats::Rats, Sprague-DawleyMedical Subject Headings::Persons::Persons::Age Groups::AdultMedical Subject Headings::Persons::Persons::Age Groups::ChildMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Cysteine Proteases::Cysteine Endopeptidases::Caspases::Caspases, Effector::Caspase 3Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell PolarityMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::GliosisMedical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::HydrocephalusMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Cell Adhesion Molecules::CadherinsMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms, Neuroepithelial::Glioma::EpendymomaMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell DifferentiationMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Spinal CordMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Microscopy::Microscopy, Electron::Microscopy, Electron, TransmissionMedical Subject Headings::Organisms::Viruses::DNA Viruses::AdenoviridaeMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell DeathMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::CytoplasmMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Cytoskeletal Proteins::CateninsMedical Subject Headings::Anatomy::Cellsresearch article34535732Acceso abierto10.1038/s41598-021-97948-32045-2322PMC8448829