Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility

Angulo-Urarte, Ana and Casado, Pedro and Castillo, Sandra D. and Kobialka, Piotr and Kotini, Maria Paraskevi and Figueiredo, Ana M. and Castel, Pau and Rajeeve, Vinothini and Milà-Guasch, Maria and Millan, Jaime and Wiesner, Cora and Serra, Helena and Muixi, Laia and Casanovas, Oriol and Viñals, Francesc and Affolter, Markus and Gerhardt, Holger and Huveneers, Stephan and Belting, Heinz-Georg and Cutillas, Pedro R. and Graupera, Mariona. (2018) Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility. Nature Communications, 9 (1). p. 4826.

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Official URL: https://edoc.unibas.ch/66836/

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Cell Biology (Affolter)
UniBasel Contributors:Affolter, Markus
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:26 Apr 2020 19:12
Deposited On:26 Apr 2020 19:12

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