Work

Robo4 Signaling in Endothelial Cells Implies Attraction Guidance Mechanisms

Year: 2006

Type: article

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.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.m508853200

Authors: Sukhbir Kaur, Maria Domenica Castellone, Victoria M. Bedell, Martha Konar, J. Silvio Gutkind, Ramani Ramchandran

Institutions: National Institutes of Health, National Cancer Institute, National Institute of Dental and Craniofacial Research

Language: English

Topic: Axon Guidance and Neuronal Signaling

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $3,430

Funders: National Institutes of Health, National Cancer Institute