Abstract 674: Vesselin Controls Vascular Morphogenesis by Activating Small Gtpases in Endothelial Cells
| العنوان: | Abstract 674: Vesselin Controls Vascular Morphogenesis by Activating Small Gtpases in Endothelial Cells |
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| المؤلفون: | Yanqing A Gong, Hao Duan, Yanling Wang, Yi Fan, Menggui Huang, Zhengqiang He |
| المصدر: | Arteriosclerosis, Thrombosis, and Vascular Biology. 38 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Vasculogenesis, medicine.anatomical_structure, Endothelium, Vascular morphogenesis, medicine, Structural integrity, GTPase, Biology, Cardiology and Cardiovascular Medicine, Wound healing, Process (anatomy), Cell biology |
| الوصف: | Vascularization is a fundamental process in development, wound healing, and the progression of cardiovascular diseases. Formation of new blood vessels with functional and structural integrity is crucial for organ growth as well as post-injury tissue repair and regeneration. Although vascular sprouting and outgrowth, i.e. , angiogenesis, has been extensively studied, the underlying mechanisms for vessel formation remain largely unexplored. Here we reveal a critical role of phosphatidylinositol 4,5-bisphosphate (PIP2) for vessel formation in endothelial cells (ECs). Moreover, by using mass spectrometry, our identified Tbc1d2b as a novel PIP2-binding protein in vessel-formatting ECs. Considering its critical function in vessel formation, we name this protein “vesselin”. We showed that vesselin preferentially localizes to blood vessels in various human tissues, and that its siRNA-mediated knockdown inhibits EC tube formation, supporting its major role in vessel formation. Remarkably, injection of inhibitory vesselin morpholino into the embryos blocks blood vessel formation and zebrafish development. Vesselin contains PH (pleckstrin homology) and TBC (Tre2/Bub2/Cdc16) domains, which are known to bind phosphatidylinositols and display GTPase-activating protein (GAP) activities towards Rab GTPases, respectively. Consistently, we found by mass spectrometry that vesselin interacts with the small GTPase Rab13 and small GTPase Rac1. Finally, our further mechanistic studies showed that vesselin interacts with Rac1 and Rab13 during EC vessel formation, and regulates their activity in a PIP2-dependent manner. Thus, we uncover a previously unidentified regulatory system for EC vessel formation, providing molecular resolution of vascular morphogenesis. Targeting vesselin may provide new therapeutic strategies in cardiovascular diseases. |
| تدمد: | 1524-4636 1079-5642 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::3c7797f66ca324eaf80d6f4f25570e2bTest https://doi.org/10.1161/atvb.38.suppl_1.674Test |
| رقم الانضمام: | edsair.doi...........3c7797f66ca324eaf80d6f4f25570e2b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244636 10795642 |
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