TMEM30A deficiency in endothelial cells impairs cell proliferation and angiogenesis

Journal of Cell Science
Shanshan ZhangXianjun Zhu

Abstract

Phosphatidylserine (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 β-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 indicate 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 ECs with fewer filopodia at the vascular front and a 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, providing a potential therapeutic target.

References

Jan 1, 1979·Annual Review of Biochemistry·J A Op den Kamp
Nov 18, 1971·The New England Journal of Medicine·J Folkman
Aug 12, 1971·The New England Journal of Medicine·J Folkman
Jun 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·M Seigneuret, P F Devaux
Nov 29, 1996·Science·S NozetteE M Shoemaker
Sep 23, 2000·Nature·P Carmeliet, R K Jain
Oct 4, 2000·Physiological Genomics·M S HalleckR A Schlegel
Feb 13, 2001·Developmental Biology·Y Y KisanukiM Yanagisawa
Sep 18, 2004·Oncology Reports·Yuriko Katoh, Masaru Katoh
Mar 2, 2005·Nature Reviews. Molecular Cell Biology·Joost C M Holthuis, Tim P Levine
May 28, 2005·Biochimica Et Biophysica Acta·C C Paulusma, R P J Oude Elferink
Apr 25, 2006·Nature Reviews. Molecular Cell Biology·Anna-Karin OlssonLena Claesson-Welsh
Oct 24, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Coen C PaulusmaRonald P J Oude Elferink
Feb 8, 2008·Genesis : the Journal of Genetics and Development·Suzanne ClaxtonMarcus Fruttiger
May 30, 2009·Proceedings of the National Academy of Sciences of the United States of America·Janneke M StapelbroekRoderick H J Houwen
Aug 5, 2010·European Journal of Human Genetics : EJHG·Pierre CacciagliLaurent Villard
Oct 16, 2010·The Journal of Biological Chemistry·Lieke M van der VeldenStan F J van de Graaf
Oct 22, 2010·The Journal of Biological Chemistry·Susanne BrydeJoost C M Holthuis
Mar 23, 2011·Nature Immunology·Owen M SiggsBruce Beutler
Apr 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Owen M SiggsBruce Beutler
Jun 30, 2011·The Biochemical Journal·Sina KochLena Claesson-Welsh
Jul 16, 2011·Annual Review of Cell and Developmental Biology·Alicia S Chung, Napoleone Ferrara
Sep 20, 2011·Cell·Michael PotentePeter Carmeliet
Jan 10, 2016·Biochimica Et Biophysica Acta·Cédric MontignyGuillaume Lenoir
Aug 26, 2017·Scientific Reports·Lin ZhangXianjun Zhu
May 8, 2018·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Dan Călugăru, Mihai Călugăru

❮ Previous
Next ❯

Citations

May 16, 2020·Critical Reviews in Biochemistry and Molecular Biology·Hye-Won Shin, Hiroyuki Takatsu
May 5, 2021·Genetic Testing and Molecular Biomarkers·Shanshan ZhangZhenglin Yang
Apr 26, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yeming YangXianjun Zhu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aneurysm

Aneurysms are outward distensions or bulges that occurs in a weakened wall of blood vessels. Discover the latest research on aneurysms here.