| Literature DB >> 28973878 |
Masahide Sakabe1,2, Jieqing Fan3,4, Yoshinobu Odaka3,4, Ning Liu5, Aishlin Hassan1,2, Xin Duan1,2, Paige Stump1,2, Luke Byerly1,2, Megan Donaldson1,2, Jiukuan Hao6, Marcus Fruttiger7, Qing Richard Lu1,2, Yi Zheng1,2, Richard A Lang3,4, Mei Xin8,2.
Abstract
Angiogenesis and vascular remodeling are essential for the establishment of vascular networks during organogenesis. Here we show that the Hippo signaling pathway effectors YAP and TAZ are required, in a gene dosage-dependent manner, for the proliferation and migration of vascular endothelial cells (ECs) during retinal angiogenesis. Intriguingly, nuclear translocation of YAP and TAZ induced by Lats1/2-deletion blocked endothelial migration and phenocopied Yap/Taz-deficient mutants. Furthermore, overexpression of a cytoplasmic form of YAP (YAPS127D) partially rescued the migration defects caused by loss of YAP and TAZ function. Finally, we found that cytoplasmic YAP positively regulated the activity of the small GTPase CDC42, deletion of which caused severe defects in endothelial migration. These findings uncover a previously unrecognized role of cytoplasmic YAP/TAZ in promoting cell migration by activating CDC42 and provide insight into how Hippo signaling in ECs regulates angiogenesis.Entities:
Keywords: CDC42; Hippo signaling; angiogenesis; cell migration
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Year: 2017 PMID： 28973878 PMCID： PMC5642684 DOI： 10.1073/pnas.1704030114
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205