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p73 regulates ependymal planar cell polarity by modulating actin and microtubule cytoskeleton

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Fuertes-Alvarez, Sandra Maeso-Alonso, Laura Villoch-Fernandez, Javier Wildung, Merit Martin-Lopez, Marta Tissir, Fadel [UCL] Marin, Maria C.

Planar cell polarity (PCP) and intercellular junctional complexes establish tissue structure and coordinated behaviors across epithelial sheets. In multiciliated ependymal cells, rotational and translational PCP coordinate cilia beating and direct cerebrospinal fluid circulation. Thus, PCP disruption results in ciliopathies and hydrocephalus. PCP establishment depends on the polarization of cytoskeleton and requires the asymmetric localization of core and global regulatory modules, including membrane proteins like Vangl1/2 or Frizzled. We analyzed the subcellular localization of select proteins that make up these modules in ependymal cells and the effect of Trp73 loss on their localization. We identify a novel function of the Trp73 tumor suppressor gene, the TAp73 isoform in particular, as an essential regulator of PCP through the modulation of actin and microtubule cytoskeleton dynamics, demonstrating that Trp73 is a key player in the organization of ependymal ciliated epithelia. Mechanistically, we show that p73 regulates translational PCP and actin dynamics through TAp73-dependent modulation of non-musclemyosin-II activity. In addition, TAp73 is required for the asymmetric localization of PCP-core and global signaling modules and regulates polarized microtubule dynamics, which in turn set up the rotational PCP. Therefore, TAp73 modulates, directly and/or indirectly, transcriptional programs regulating actin and microtubules dynamics and Golgi organization signaling pathways. These results shed light into the mechanism of ependymal cell planar polarization and reveal p73 as an epithelial architect during development regulating the cellular cytoskeleton.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2018
Language Anglais
Journal information "Cell Death & Disease" - Vol. 9, no.1183 (2018)
Publisher Springer Nature
e-issn 2041-4889
Publication status Publié
Affiliation UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
Keywords Immunology ; Cell Biology ; Cancer Research ; Cellular and Molecular Neuroscience
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Bibliographic reference Fuertes-Alvarez, Sandra ; Maeso-Alonso, Laura ; Villoch-Fernandez, Javier ; Wildung, Merit ; Martin-Lopez, Marta ; et. al. p73 regulates ependymal planar cell polarity by modulating actin and microtubule cytoskeleton. In: Cell Death & Disease, Vol. 9, no.1183 (2018)
Permanent URL http://hdl.handle.net/2078.1/212396