TY - JOUR
T1 - C terminus of RGS-GAIP-interacting protein conveys neuropilin-1-mediated signaling during angiogenesis
AU - Wang, Ling
AU - Mukhopadhyay, Debabrata
AU - Xu, Xiaolei
PY - 2006/7
Y1 - 2006/7
N2 - Initially, it was thought that there was no intracellular signaling mediated by NRP-1 alone in response to its ligands. However, the emerging data from our group as well as others suggest that the signaling through NRP-1 actually promotes angiogenesis and is mediated through its C-terminal domain and downstream molecules such as phosphoinositide 3-kinase. Hence, understanding the signal transduction pathways mediated by NRP-1 and identification of its downstream molecules are of importance. By using both in vivo zebrafish model and in vitro tissue culture system, we have shown that the C-terminal three amino acids of NRP-1 (SEA-COOH) are required for NRP-1-mediated angiogenesis. Furthermore, knocking down of RGS-GAIP-interacting protein C terminus (GIPC) in zebrafish, which is associated with C-terminal domain of NRP-1, exhibits similar vasculature phenotypes to those from NRP-1 null. Specific and effective silencing of GIPC in vascular endothelium results in inhibition of NRP-1-mediated migration. In both cases as described, PDZ domain of GIPC is responsible for its function. Taken together, our data suggest a novel role of GIPC in angiogenesis and vessel formation and also support our hypothesis that NRP-1 can facilitate downstream signaling to promote angiogenesis through GIPC.
AB - Initially, it was thought that there was no intracellular signaling mediated by NRP-1 alone in response to its ligands. However, the emerging data from our group as well as others suggest that the signaling through NRP-1 actually promotes angiogenesis and is mediated through its C-terminal domain and downstream molecules such as phosphoinositide 3-kinase. Hence, understanding the signal transduction pathways mediated by NRP-1 and identification of its downstream molecules are of importance. By using both in vivo zebrafish model and in vitro tissue culture system, we have shown that the C-terminal three amino acids of NRP-1 (SEA-COOH) are required for NRP-1-mediated angiogenesis. Furthermore, knocking down of RGS-GAIP-interacting protein C terminus (GIPC) in zebrafish, which is associated with C-terminal domain of NRP-1, exhibits similar vasculature phenotypes to those from NRP-1 null. Specific and effective silencing of GIPC in vascular endothelium results in inhibition of NRP-1-mediated migration. In both cases as described, PDZ domain of GIPC is responsible for its function. Taken together, our data suggest a novel role of GIPC in angiogenesis and vessel formation and also support our hypothesis that NRP-1 can facilitate downstream signaling to promote angiogenesis through GIPC.
KW - Endothelial cells
KW - NRP-1
KW - PDZ-domain
KW - VPF/VEGF
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=33845678052&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845678052&partnerID=8YFLogxK
U2 - 10.1096/fj.05-5504fje
DO - 10.1096/fj.05-5504fje
M3 - Article
C2 - 16754745
AN - SCOPUS:33845678052
SN - 0892-6638
VL - 20
SP - E732-E741
JO - FASEB Journal
JF - FASEB Journal
IS - 9
ER -