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Robo4 signaling in endothelial cells implies attraction guidance mechanisms. J Biol Chem 2006 Apr 21;281(16):11347-56

Date

02/17/2006

Pubmed ID

16481322

DOI

10.1074/jbc.M508853200

Abstract

Roundabouts (robo) are cell-surface receptors that mediate repulsive signaling mechanisms at the central nervous system midline. However, robos may also mediate attraction mechanisms in the context of vascular development. Here, we have performed structure-function analysis of roundabout4 (Robo4), the predominant robo expressed in embryonic zebrafish vasculature and found by gain of function approaches in vitro that Robo4 activates Cdc42 and Rac1 Rho GTPases in endothelial cells. Indeed, complementary robo4 gene knockdown approaches in zebrafish embryos show lower amounts of active Cdc42 and Rac1 and angioblasts isolated from these knockdown embryos search actively for directionality and guidance cues. Furthermore, Robo4-expressing endothelial cells show morphology and phenotype, characteristic of Rho GTPase activation. Taken together, this study suggests that Robo4 mediates attraction-signaling mechanisms through Rho GTPases in vertebrate vascular guidance.

Author List

Kaur S, Castellone MD, Bedell VM, Konar M, Gutkind JS, 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

Animals
Blotting, Western
Cell Adhesion
Cell Line
Cell Membrane
Cell Movement
Cloning, Molecular
Endothelial Cells
GTP Phosphohydrolases
Gene Expression Regulation, Developmental
Image Processing, Computer-Assisted
Microscopy, Confocal
Models, Genetic
Mutation
Neovascularization, Physiologic
Nucleotides
Phenotype
Protein Binding
Protein Structure, Tertiary
Pseudopodia
RNA
Receptors, Cell Surface
Signal Transduction
Time Factors
Transfection
Zebrafish
Zebrafish Proteins
cdc42 GTP-Binding Protein
rac1 GTP-Binding Protein
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d