Ninein Is Expressed in the Cytoplasm of Angiogenic Tip-Cells and Regulates Tubular Morphogenesis of Endothelial Cells
2008 (English)In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, Vol. 28, 2123-2130 p.Article in journal (Refereed) Published
Objective— Angiogenesis is an integral part of many physiological processes but may also aggravate pathological conditions such as cancer. Development of effective angiogenesis inhibitors requires a thorough understanding of the molecular mechanisms regulating vessel formation. The aim of this project was to identify proteins that regulate tubular morphogenesis of endothelial cells.
Methods and Results— Phosphotyrosine-dependent affinity-purification and mass spectrometry showed tyrosine phosphorylation of ninein during tubular morphogenesis of endothelial cells. Ninein was recently identified as a centrosomal microtubule-anchoring protein. Our results show that ninein is localized in the cytoplasm in endothelial cells, and that it is highly expressed in the vasculature in normal and pathological human tissues. Using embryoid bodies as a model of vascular development, we found that ninein is abundantly expressed in the cytoplasm of endothelial cells during sprouting angiogenesis, in particular in the sprouting tip-cell. In accordance, siRNA-dependent silencing of ninein in endothelial cells inhibited tubular morphogenesis.
Conclusions— In this study, we show that ninein is expressed in developing vessels and in endothelial tip cells, and that ninein is critical for formation of the vascular tube. These data strongly implicate ninein as an important new regulator of angiogenesis.
Proteins orchestrating morphological changes accompanying formation of the vascular tube constitute new targets for antiangiogenic therapy. In this study, we identify the microtubule-anchoring protein ninein as an important new regulator of tubular morphogenesis of endothelial cells. This is the first report of a functional role of ninein in angiogenesis.
Place, publisher, year, edition, pages
2008. Vol. 28, 2123-2130 p.
ninein, angiogenesis, tubular morphogenesis, microtubule, endothelial
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-87342DOI: 10.1161/ATVBAHA.108.169128ISI: 000261031200008OAI: oai:DiVA.org:uu-87342DiVA: diva2:37342