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Título
p73 regulates ependymal planar cell polarity by modulating actin and microtubule cytoskeleton
Autor
Facultad/Centro
Área de conocimiento
Título de la revista
Cell Death and Disease
Número de la revista
12
Cita Bibliográfica
Fuertes-Alvarez, S., Maeso-Alonso, L., Villoch-Fernandez, J., Wildung, M., Martin-Lopez, M., Marshall, C., Villena-Cortes, A. J., Diez-Prieto, I., Pietenpol, J. A., Tissir, F., Lizé, M., Marques, M. M., & Marin, M. C. (2018). p73 regulates ependymal planar cell polarity by modulating actin and microtubule cytoskeleton. Cell Death and Disease, 9(12). https://doi.org/10.1038/S41419-018-1205-6
Editorial
Springer Nature
Fecha
2018
Resumen
[EN]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
Materia
Palabras clave
Peer review
SI
ID proyecto
- info:eu-repo/grantAgreement/MINECO/Programa Estatal de I+D+I Orientada a los Retos de la Sociedad/SAF2015-71381-R/ES/ANALISIS DE LA INTERACCION YIN-YANG ENTRE TP53 Y TP73 EN LA REPROGRAMACION Y ARQUITECTURA TISULAR: IMPLICACION EN ONCOGENESIS TUMORAL
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