2026-04-13T15:13:10Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1334502025-12-05T09:21:38Zcom_2072_1057col_2072_478799col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Angulo Urarte, Ana author Casado, Pedro author Castillo, Sandra D. author Kobialka, Piotr author Kotini, Maria Paraskevi author Figueiredo, Ana Raquel Martins author Castel Morales, Pau author Rajeeve, Vinothini author Milà Guasch, Maria author Millán, Jaime author Wiesner, Cora author Serra, Helena author Muixi, Laura author Casanovas i Casanovas, Oriol author Viñals Canals, Francesc author Affolter, Markus author Gerhardt, Holger author Huveneers, Stephan author Belting, Heinz-Georg author Cutillas, Pedro R. author Graupera i Garcia-Milà, Mariona author 2019-05-20T11:53:40Z 2019-05-20T11:53:40Z 2018-11-16 2019-05-20T11:53:40Z 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. Proteïnes quinases Angiogènesi Regulació genètica Expressió gènica Protein kinases Neovascularization Genetic regulation Gene expression Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility