Format

Send to

Choose Destination
Development. 2014 Apr;141(7):1465-72. doi: 10.1242/dev.104539. Epub 2014 Mar 5.

Dynamin 2 regulation of integrin endocytosis, but not VEGF signaling, is crucial for developmental angiogenesis.

Author information

1
Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.

Abstract

Here we show that dynamin 2 (Dnm2) is essential for angiogenesis in vitro and in vivo. In cultured endothelial cells lacking Dnm2, vascular endothelial growth factor (VEGF) signaling and receptor levels are augmented whereas cell migration and morphogenesis are impaired. Mechanistically, the loss of Dnm2 increases focal adhesion size and the surface levels of multiple integrins and reduces the activation state of β1 integrin. In vivo, the constitutive or inducible loss of Dnm2 in endothelium impairs branching morphogenesis and promotes the accumulation of β1 integrin at sites of failed angiogenic sprouting. Collectively, our data show that Dnm2 uncouples VEGF signaling from function and coordinates the endocytic turnover of integrins in a manner that is crucially important for angiogenesis in vitro and in vivo.

KEYWORDS:

Angiogenesis; Endocytosis; Endothelium; Mouse

PMID:
24598168
PMCID:
PMC3957370
DOI:
10.1242/dev.104539
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center