Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/133450
Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
Angiogenesis is a dynamic process relying on endothelial cell rearrangements within vascular tubes, yet the underlying mechanisms and functional relevance are poorly understood. Here we show that PI3Kα regulates endothelial cell rearrangements using a combination of a PI3Kα-selective inhibitor and endothelial-specific genetic deletion to abrogate PI3Kα activity during vessel development. Quantitative phosphoproteomics together with detailed cell biology analyses in vivo and in vitro reveal that PI3K signalling prevents NUAK1-dependent phosphorylation of the myosin phosphatase targeting-1 (MYPT1) protein, thereby allowing myosin light chain phosphatase (MLCP) activity and ultimately downregulating actomyosin contractility. Decreased PI3K activity enhances actomyosin contractility and impairs junctional remodelling and stabilization. This leads to overstretched endothelial cells that fail to anastomose properly and form aberrant superimposed layers within the vasculature. Our findings define the PI3K/NUAK1/MYPT1/MLCP axis as a critical pathway to regulate actomyosin contractility in endothelial cells, supporting vascular patterning and expansion through the control of cell rearrangement.
Matèries (anglès)
Citació
Citació
ANGULO URARTE, Ana, CASADO, Pedro, CASTILLO, Sandra d., KOBIALKA, Piotr, KOTINI, Maria paraskevi, FIGUEIREDO, Ana raquel martins, CASTEL MORALES, Pau, RAJEEVE, Vinothini, MILÀ GUASCH, Maria, MILLÁN, Jaime, WIESNER, Cora, SERRA, Helena, MUIXI, Laura, CASANOVAS I CASANOVAS, Oriol, VIÑALS CANALS, Francesc, AFFOLTER, Markus, GERHARDT, Holger, HUVENEERS, Stephan, BELTING, Heinz-georg, CUTILLAS, Pedro r., GRAUPERA I GARCIA-MILÀ, Mariona. Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility. _Nature Communications_. 2018. Vol. 9, núm. 1, pàgs. 4826. [consulta: 2 de febrer de 2026]. ISSN: 2041-1723. [Disponible a: https://hdl.handle.net/2445/133450]