Date of Award
Doctor of Philosophy (PhD)
Cancer and Developmental Biology
Xin A. Zhang, M.D., Ph.D.
Suzanne J. Baker, Ph.D. Jill M. Lahti, Ph.D. Anjaparavanda P. Naren, Ph.D. Lawrence M. Pfeffer, Ph.D.
Tetraspanin CD151 is highly expressed in endothelial cells and regulates pathological angiogenesis. However, the mechanism by which CD151 promotes vascular morphogenesis and whether CD151 engages other vascular functions are unclear. We observed that CD151 is required for the maintenance of endothelial capillary-like structures formed in vitro and the integrity of lung endothelial cell-cell contacts in vivo. As a master regulator of endothelial cell-matrix and cell-cell adhesions, CD151 is needed for the optimal functions of various cell adhesion proteins such as integrin, cadherin, and CD44. The loss of CD151 elevates the cellular intrinsic contraction by upregulating RhoA signaling and downregulating of Rac1 activity. CD151 balances RhoA and Rac1 activities and stabilizes the membrane-cytoskeleton connection. In the absence of CD151 expression, the inhibition of RhoA signaling axis enhances the diminished cell-cell adhesiveness and stabilizes vascular structures. In addition, CD151-dependent vascular stabilization involves cAMP signaling and might thus regulate RhoA and Rac1. Together, CD151 reinforces vascular stability by promoting endothelial cell-matrix and cell-cell adhesions to counterbalance the destabilization derived from RhoAsignaling-mediated cytoskeletal tension.
Zhang, Feng , "CD151 Reinforces Vascular Stability by Balancing Endothelial Cell Adhesion and Cytoskeletal Tension" (2010). Theses and Dissertations (ETD). Paper 322. http://dx.doi.org/10.21007/etd.cghs.2010.0374.