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Title: | Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility |
Author: | 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 |
Keywords: | Proteïnes quinases Angiogènesi Regulació genètica Expressió gènica Protein kinases Neovascularization Genetic regulation Gene expression |
Issue Date: | 16-Nov-2018 |
Publisher: | Nature Publishing Group |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41467-018-07172-3 |
It is part of: | Nature Communications, 2018, vol. 9, num. 1, p. 4826 |
URI: | http://hdl.handle.net/2445/133450 |
Related resource: | https://doi.org/10.1038/s41467-018-07172-3 |
ISSN: | 2041-1723 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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