Open AccessTmem30a Deficiency in endothelial cells impairs cell proliferation and angiogenesis
Author(s) -
Shanshan Zhang,
Wenjing Liu,
Yeming Yang,
Kuanxiang Sun,
Shujin Li,
Huijuan Xu,
Yang Mu,
Lin Zhang,
Xianjun Zhu
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.225052
Subject(s) - biology , angiogenesis , microbiology and biotechnology , endothelial stem cell , cell growth , cancer research , immunology , genetics , in vitro
Phosphatidylserine (PS) is PS asymmetry in the eukaryotic cell membrane is maintained by a group of proteins belonging to the P4-ATPase family, namely, PS flippases. The folding and transporting of P4-ATPases to their cellular destination requires a beta-subunit member of the TMEM30 protein family. Loss of Tmem30a has been shown to cause multiple disease conditions. However, its roles in vascular development have not been elucidated. Here, we show that TMEM30A plays critical roles in retinal vascular angiogenesis, which is a fundamental process in vascular development. Our data indicated that knockdown of TMEM30A in primary human retinal endothelial cells led to reduced tube formation. In mice, endothelial cell (EC)-specific deletion of Tmem30a led to retarded retinal vascular development with a hyperpruned vascular network as well as blunted-end, aneurysm-like tip endothelial cells (ECs) with fewer filopodia at the vascular front and reduced number of tip cells. Deletion of Tmem30a also impaired vessel barrier integrity. Mechanistically, deletion of TMEM30A caused reduced EC proliferation by inhibiting VEGF-induced signaling. Our findings reveal essential roles of TMEM30A in angiogenesis, and providing a potential therapeutic target.