PUBLICATION
Robo4 signaling in endothelial cells imply attraction guidance mechanisms
- Authors
- Kaur, S., Castellone, M.D., Bedell, V.M., Konar, M., Gutkind, J.S., and Ramchandran, R.
- ID
- ZDB-PUB-060227-4
- Date
- 2006
- Source
- The Journal of biological chemistry 281(16): 11347-11356 (Journal)
- Registered Authors
- Ramchandran, Ramani
- Keywords
- none
- MeSH Terms
-
- Animals
- Blotting, Western
- Cell Adhesion
- Cell Line
- Cell Membrane/metabolism
- Cell Movement
- Cloning, Molecular
- Endothelial Cells/metabolism*
- GTP Phosphohydrolases/metabolism
- Gene Expression Regulation, Developmental*
- Image Processing, Computer-Assisted
- Microscopy, Confocal
- Models, Genetic
- Mutation
- Neovascularization, Physiologic
- Nucleotides/chemistry
- Phenotype
- Protein Binding
- Protein Structure, Tertiary
- Pseudopodia/metabolism
- RNA/metabolism
- Receptors, Cell Surface/metabolism
- Receptors, Cell Surface/physiology*
- Signal Transduction
- Time Factors
- Transfection
- Zebrafish
- Zebrafish Proteins/metabolism
- Zebrafish Proteins/physiology*
- cdc42 GTP-Binding Protein/metabolism
- rac1 GTP-Binding Protein/metabolism
- PubMed
- 16481322 Full text @ J. Biol. Chem.
Citation
Kaur, S., Castellone, M.D., Bedell, V.M., Konar, M., Gutkind, J.S., and Ramchandran, R. (2006) Robo4 signaling in endothelial cells imply attraction guidance mechanisms. The Journal of biological chemistry. 281(16):11347-11356.
Abstract
Roundabouts (robo) are cell surface receptors that mediate repulsive signaling mechanisms at the CNS 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. Further, 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping