C terminus of RGS-GAIP-interacting protein conveys neuropilin-1-mediated signaling during angiogenesis.
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.
Wang
Ling
L
Department Biochemistry and Molecular Biology, Gugg 1401A, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, Minnesota 55905, USA.
Mukhopadhyay
Debabrata
D
Xu
Xiaolei
X
D000818:Animals; D002478:Cells, Cultured; D017124:Conserved Sequence; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D018919:Neovascularization, Physiologic; D039942:Neuropilin-1 / Q000502:physiology*; D020710:RGS Proteins / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D012326:RNA Splicing; D015398:Signal Transduction / Q000502:physiology*; D014471:Umbilical Veins; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000502:physiology
D009025:Morpholines; D020710:RGS Proteins; D029961:Zebrafish Proteins; C097187:regulator of G-protein signalling 19; D039942:Neuropilin-1