Syx, a RhoA guanine exchange factor, is essential for angiogenesis in Vivo.
Syx, a RhoA guanine exchange factor, is essential for angiogenesis in Vivo.
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DOI：
10.1161/circresaha.108.181388
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发表时间：
2008-09-26
影响因子：
20.1
通讯作者：
Ramchandran R
中科院分区：
文献类型：
--
作者：
Garnaas MK;Moodie KL;Liu ML;Samant GV;Li K;Marx R;Baraban JM;Horowitz A;Ramchandran R
Rho GTP酶在多种生物学过程中发挥着重要而广泛的作用。在本研究中，我们鉴定了哺乳动物Rho A鸟氨酸交换因子的同源基因--聚合素结合的gef(Syx)，并测定了其在斑马鱼和小鼠体内的功能。我们发现Syx在这些生物的血管系统中特异表达。斑马鱼和小鼠的功能丧失研究指出，在发育中的血管床中，Syx在血管新生萌发中扮演着特定的角色。重要的是，融合基因敲除斑马鱼胚胎中的血管生成和血管母细胞分化步骤不受影响，而血管萌发缺陷可以被小鼠同源基因部分修复。Syx KD体外抑制血管内皮生长因子-A(VEGF-A)诱导的内皮细胞迁移和血管生成。我们还发现了一种潜在的内皮萌发引导机制，在这种机制中，内皮细胞连接的一种成分Angiomotin(AMOT)与Syx在指导内皮萌发方面起到了相加的作用。这些结果证实Syx是体内血管生成的重要贡献者。
Rho GTPases play an important and versatile role in several biological processes. In this study, we identified the zebrafish ortholog of the mammalian Rho A guanine exchange factor (GEF), Synectin-binding GEF (Syx), and determined its in vivo function in the zebrafish and the mouse. We found that Syx is expressed specifically in the vasculature of these organisms. Loss-of-function studies in the zebrafish and mouse point to a specific role for Syx in angiogenic sprouting in the developing vascular bed. Importantly, vasculogenesis and angioblast differentiation steps were unaffected in syx-knockdown (KD) zebrafish embryos, and the vascular sprouting defects were partially rescued by the mouse ortholog. Syx KD in vitro impairs vascular endothelial growth factor-A (VEGF-A) induced endothelial cell migration and angiogenesis. We have also uncovered a potential mechanism of endothelial sprout guidance in which Angiomotin (Amot), a component of endothelial cell junctions, plays an additive role with Syx in directing endothelial sprouts. These results identify Syx as an essential contributor to angiogenesis in vivo.