ZFIN ID: ZDB-PUB-060616-33
C terminus of RGS-GAIP-interacting protein conveys neuropilin-1-mediated signaling during angiogenesis
Wang, L., Mukhopadhyay, D., and Xu, X.
Date: 2006
Source: FASEB journal : official publication of the Federation of American Societies for Experimental Biology   20(9): 1513-1515 (Journal)
Registered Authors: Xu, Xiaolei
Keywords: none
MeSH Terms:
  • Animals
  • Cells, Cultured
  • Conserved Sequence
  • Endothelium, Vascular/drug effects
  • Endothelium, Vascular/physiology*
  • Humans
  • Morpholines/pharmacology
  • Neovascularization, Physiologic*
  • Neuropilin-1/physiology*
  • RGS Proteins/genetics
  • RGS Proteins/physiology*
  • RNA Interference
  • RNA Splicing
  • Signal Transduction/physiology*
  • Umbilical Veins
  • Zebrafish
  • Zebrafish Proteins/physiology
PubMed: 16754745 Full text @ FASEB J.
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ABSTRACT
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, L., Mukhopadhyay, D., Xu, X. C terminus of RGS-GAIP-interacting protein conveys neuropilin-1-mediated signaling during angiogenesis.
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