Liu, Miaoliang
Mayo Clinic
Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756 2
Citations 2
VEGF and Angiopoietin-1 exert opposing effects on cell junctions by regulating the Rho GEF Syx
Ngok, Siu P., Geyer, Rory, Liu, Miaoliang, Kourtidis, Antonis , Agrawal, Sudesh, Wu, Chuanshen, Seerapu, Himabindu Reddy, Lewis‐Tuffin, Laura J. , Moodie, Karen L , Deborah, Huveldt, Marx, Ruth, Baraban, Jay M. , Störz, Peter , Horowitz, Arie , Anastasiadis, Panos Z.
Journal of Cell Biology | December 17, 2012 | Volume: 199 | Issue: 7 | Pages: 1103-1115
Vascular endothelial growth factor (VEGF) and Ang1 (Angiopoietin-1) have opposing effects on vascular permeability, but the molecular basis of these effects is not fully known. We report in this paper that VEGF and Ang1 regulate endothelial cell (EC) junctions by determining the localization of the RhoA-specific guanine nucleotide exchange factor Syx. Syx was recruited to junctions by members of the Crumbs polarity complex and promoted junction integrity by activating Diaphanous. VEGF caused translocation of Syx from cell junctions, promoting junction disassembly, whereas Ang1 maintained Syx at the junctions, inducing junction stabilization. The VEGF-induced translocation of Syx from EC junctions was caused by PKD1 (protein kinase D1)-mediated phosphorylation of Syx at Ser806, which reduced Syx association to its junctional anchors. In support of the pivotal role of Syx in regulating EC junctions, syx−/− mice had defective junctions, resulting in vascular leakiness, edema, and impaired heart function.
Vascular Endothelial Growth Factor and Semaphorin Induce Neuropilin-1 Endocytosis via Separate Pathways
Salikhova, Anna Y. , Lanahan, Anthony A., Liu, Miaoliang, Simons, Michael , Leenders, William P. J. , Horowitz, Arie , Wang, Ling , Mukhopadhyay, Debabrata , Simons, Michael
Circulation Research | August 22, 2008 | Volume: 103 | Issue: 6 | Pages: No page available
The neuropilin (Nrp)1 receptor is essential for both nervous and vascular system development. Nrp1 is unusually versatile, because it transmits both chemoattractive and repulsive signals in response to vascular endothelial growth factor (VEGF)-A and class 3 semaphorins, respectively. Both Nrp1 and VEGF receptor 2 undergo ligand-dependent endocytosis. We sought to establish the endocytic pathway of Nrp1 and to determine whether uptake is required for its signaling. Whereas Nrp1 underwent clathrin-dependent endocytosis in response to VEGFA 165 treatment, semaphorin 3C (sema3C) induced lipid raft–dependent endocytosis. The myosin VI PDZ (postsynaptic density 95, Disk large, Zona occludens-1) adaptor protein synectin was essential for Nrp1 trafficking. Sema3C failed to inhibit migration of synectin −/− endothelial cells, mirroring the lower migratory response of these cells to VEGFA 165 . These results show that the endocytic pathway of Nrp1 is determined by its ligand and that the trafficking of Nrp1 is essential for its signaling.