RT info:eu-repo/semantics/article
T1 p73 is required for vessel integrity controlling endothelial junctional dynamics through Angiomotin
A1 Maeso Alonso, Laura
A1 Alonso-Olivares, Hugo
A1 Martínez-García, Nicole
A1 López-Ferreras, Lorena
A1 Villoch-Fernández, Javier
A1 Puente-Santamaría, Laura
A1 Colas-Algora, Natalia
A1 Fernández-Corona, Alfonso
A1 Lorenzo-Marcos, María Elena
A1 Jiménez, Benilde
A1 Holmgren, Lars
A1 Wilhelm, Margareta
A1 Millan, Jaime
A1 del Peso, Luis
A1 Claesson-Welsh, Lena
A1 Marqués Martínez, Margarita
A1 Marín Vieira, María Carmen
A2 Bioquimica y Biologia Molecular
K1 Biología
K1 p53 family
K1 Cell junctions
K1 Endothelial barrier integrity
K1 Vascular morphogenesis
K1 Actin cytoskeleton
K1 VE-cadherin and angiogenesis
K1 2415 Biología Molecular
AB [EN] Preservation of blood vessel integrity, which is critical for normal physiology and organ function, is controlled at multiple levels, including endothelial junctions. However, the mechanism that controls the adequate assembly of endothelial cell junctions is not fully defined. Here, we uncover TAp73 transcription factor as a vascular architect that orchestrates transcriptional programs involved in cell junction establishment and developmental blood vessel morphogenesis and identify Angiomotin (AMOT) as a TAp73 direct transcriptional target. Knockdown of p73 in endothelial cells not only results in decreased Angiomotin expression and localization at intercellular junctions, but also affects its downstream function regarding Yes-associated protein (YAP) cytoplasmic sequestration upon cell–cell contact. Analysis of adherens junctional morphology after p73-knockdown in human endothelial cells revealed striking alterations, particularly a sharp increase in serrated junctions and actin bundles appearing as stress fibers, both features associated with enhanced barrier permeability. In turn, stabilization of Angiomotin levels rescued those junctional defects, confirming that TAp73 controls endothelial junction dynamics, at least in part, through the regulation of Angiomotin. The observed defects in monolayer integrity were linked to hyperpermeability and reduced transendothelial electric resistance. Moreover, p73-knockout retinas showed a defective sprout morphology coupled with hemorrhages, highlighting the physiological relevance of p73 regulation in the maintenance of vessel integrity in vivo. We propose a new model in which TAp73 acts as a vascular architect integrating transcriptional programs that will impinge with Angiomotin/YAP signaling to maintain junctional dynamics and integrity, while balancing endothelial cell rearrangements in angiogenic vessels.
PB Springer
SN 1420-682X
LK http://hdl.handle.net/10612/15156
UL http://hdl.handle.net/10612/15156
NO Maeso-Alonso, L., Alonso-Olivares, H., Martínez-García, N. et al. p73 is required for vessel integrity controlling endothelial junctional dynamics through Angiomotin. Cell. Mol. Life Sci. 79, 535 (2022). https://doi.org/10.1007/s00018-022-04560-3
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 26-abr-2024