共 36 条
Robo4 signaling in endothelial cells implies attraction guidance mechanisms
被引:69
作者:

Kaus, S
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机构: NIH, Pathol Lab, NCI, Rockville, MD 20850 USA

Castellone, MD
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机构: NIH, Pathol Lab, NCI, Rockville, MD 20850 USA

Bedell, VM
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机构: NIH, Pathol Lab, NCI, Rockville, MD 20850 USA

Konar, M
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机构: NIH, Pathol Lab, NCI, Rockville, MD 20850 USA

Gutkind, JS
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机构: NIH, Pathol Lab, NCI, Rockville, MD 20850 USA

Ramchandran, R
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机构: NIH, Pathol Lab, NCI, Rockville, MD 20850 USA
机构:
[1] NIH, Pathol Lab, NCI, Rockville, MD 20850 USA
[2] NIDCR, Cell Growth Regulat Sect, Oral & Pharyngeal Canc Branch, NIH, Rockville, MD 20850 USA
关键词:
D O I:
10.1074/jbc.M508853200
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
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.
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页码:11347 / 11356
页数:10
相关论文
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