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Silencing of directional migration in roundabout4 knockdown endothelial cells. BMC Cell Biol 2008 Nov 03;9:61

Date

11/05/2008

Pubmed ID

18980679

Pubmed Central ID

PMC2613885

DOI

10.1186/1471-2121-9-61

Scopus ID

2-s2.0-58149397961 (requires institutional sign-in at Scopus site)   42 Citations

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 have investigated gene knockdown analysis of endothelial Robos, in particular roundabout 4 (robo4), the predominant Robo in endothelial cells using small interfering RNA technology in vitro.

RESULTS: Robo1 and Robo4 knockdown cells display distinct activity in endothelial cell migration assay. The knockdown of robo4 abrogated the chemotactic response of endothelial cells to serum but enhanced a chemokinetic response to Slit2, while robo1 knockdown cells do not display chemotactic response to serum or VEGF. Robo4 knockdown endothelial cells unexpectedly show up regulation of Rho GTPases. Zebrafish Robo4 rescues both Rho GTPase homeostasis and serum reduced chemotaxis in robo4 knockdown cells. Robo1 and Robo4 interact and share molecules such as Slit2, Mena and Vilse, a Cdc42-GAP. 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.

CONCLUSION: This study identifies specific components of the Robo signaling apparatus that work together to guide directional migration of endothelial cells.

Author List

Kaur S, Samant GV, Pramanik K, Loscombe PW, Pendrak ML, Roberts DD, Ramchandran R

Author

Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Cell Movement
Cells, Cultured
Chemotaxis
Endothelial Cells
Gene Silencing
Humans
Intercellular Signaling Peptides and Proteins
Nerve Tissue Proteins
RNA
RNA, Small Interfering
Receptors, Cell Surface
Receptors, Immunologic
Serum
cdc42 GTP-Binding Protein
rho GTP-Binding Proteins