Author/Authors :
Katrien De Bock، نويسنده , , Maria Georgiadou، نويسنده , , Sandra Schoors، نويسنده , , Anna Kuchnio، نويسنده , , Brian W. Wong، نويسنده , , Anna Rita Cantelmo، نويسنده , , Annelies Quaegebeur، نويسنده , , Bart Ghesquiere، نويسنده , , Sandra Cauwenberghs، نويسنده , , Guy Eelen، نويسنده , , Li-Kun Phng، نويسنده , , Inge Betz، نويسنده , , Bieke Tembuyser، نويسنده , , Katleen Brepoels، نويسنده , , Jonathan Welti، نويسنده , , Ilse Geudens، نويسنده , , Inmaculada Segura، نويسنده , , Bert Cruys، نويسنده , , Franscesco Bifari، نويسنده , , Ilaria Decimo، نويسنده , , et al.، نويسنده ,
Abstract :
Vessel sprouting by migrating tip and proliferating stalk endothelial cells (ECs) is controlled by genetic signals (such as Notch), but it is unknown whether metabolism also regulates this process. Here, we show that ECs relied on glycolysis rather than on oxidative phosphorylation for ATP production and that loss of the glycolytic activator PFKFB3 in ECs impaired vessel formation. Mechanistically, PFKFB3 not only regulated EC proliferation but also controlled the formation of filopodia/lamellipodia and directional migration, in part by compartmentalizing with F-actin in motile protrusions. Mosaic in vitro and in vivo sprouting assays further revealed that PFKFB3 overexpression overruled the pro-stalk activity of Notch, whereas PFKFB3 deficiency impaired tip cell formation upon Notch blockade, implying that glycolysis regulates vessel branching.
