PUBLICATION

Silencing Of Directional Migration In Roundabout4 Knockdown Endothelial Cells

Authors
Kaur, S., Samant, G.V., Pramanik, K., Loscombe, P.W., Pendrak, M.L., Roberts, D.D., and Ramchandran, R.
ID
ZDB-PUB-081105-17
Date
2008
Source
BMC Cell Biology   9: 61 (Journal)
Registered Authors
Ramchandran, Ramani
Keywords
none
MeSH Terms
  • Cell Movement
  • Cells, Cultured
  • Chemotaxis
  • Endothelial Cells/cytology
  • Endothelial Cells/metabolism*
  • Gene Silencing
  • Humans
  • Intercellular Signaling Peptides and Proteins/metabolism
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism
  • RNA/metabolism
  • RNA, Small Interfering/genetics*
  • Receptors, Cell Surface/genetics*
  • Receptors, Cell Surface/metabolism*
  • Receptors, Immunologic/genetics
  • Receptors, Immunologic/metabolism
  • Serum/metabolism
  • cdc42 GTP-Binding Protein/metabolism
  • rho GTP-Binding Proteins/metabolism
PubMed
18980679 Full text @ BMC Cell Biol.
Abstract
BACKGROUND: Roundabouts are axon guidance molecules that have recently been identified to play a role in vascular guidance as well. In this study, we investigated gene knockdown analysis of roundabout 4 (robo4), the predominant Robo in endothelial cells using small interfering RNA technology in vitro. RESULTS: Robo4 knockdown abrogated the chemotactic response of endothelial cells to serum but enhanced a chemokinetic response to slit2. Robo4 knockdown endothelial cells unexpectedly show up regulation of Rho GTPases. Zebrafish robo4 rescues both Rho GTPase homeostasis and serum induced chemotaxis in robo4 knockdown cells. In addition, this study mechanistically implicates IRSp53 in the signaling nexus between activated Cdc42 and Mena, both of which have previously been shown to be involved with robo4 signaling in endothelial cells. CONCLUSIONS: This work for the first time provides components of the robo4 signaling apparatus that work together to guide directional migration of endothelial cells.
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