Endothelial cell-specific chemotaxis receptor (ecscr) promotes angioblast migration during vasculogenesis and enhances VEGF receptor sensitivity.
Endothelial cell-specific chemotaxis receptor (ecscr) promotes angioblast migration during vasculogenesis and enhances VEGF receptor sensitivity.
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DOI：
10.1182/blood-2009-10-248856
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发表时间：
2010-06
期刊：
影响因子：
20.3
通讯作者：
A. Verma;Resham Bhattacharya;Indulekha Remadevi;Keguo Li;K. Pramanik;G. V. Samant;Mark A Horswill;C. Chun;Baofeng Zhao;E. Wang;R. Miao;D. Mukhopadhyay;R. Ramchandran;G. Wilkinson
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作者：
A. Verma;Resham Bhattacharya;Indulekha Remadevi;Keguo Li;K. Pramanik;G. V. Samant;Mark A Horswill;C. Chun;Baofeng Zhao;E. Wang;R. Miao;D. Mukhopadhyay;R. Ramchandran;G. Wilkinson
内皮细胞特异性趋化性受体（ECSCR）是由血液内皮细胞表达的一种细胞表面蛋白，在内皮细胞迁移和信号转导中起作用。我们研究了内皮细胞前胶原受体在斑马鱼血管发育中的作用。斑马鱼ecscr在成血管细胞迁移和血管发生过程中在成血管细胞和轴向血管中表达。吗啉代导向的ecscr敲低导致后侧板中胚层中成血管细胞迁移缺陷，这一过程依赖于血管内皮源性生长因子（VEGF）。在培养的细胞中，转染的ECSCR定位于肌动蛋白丰富的膜突起，共定位与激酶插入结构域蛋白受体（KDR）/VEGF受体2在这些地区。ECSCR沉默的细胞显示VEGF诱导的KDR磷酸化降低，但FMS样酪氨酸激酶1（FLT 1）/VEGF受体1的磷酸化没有降低。最后，斑马鱼中VEGF受体活性的化学抑制导致成血管细胞缺陷，其与ecscr morphants中所见的缺陷部分重叠。我们建议，ecscr促进迁移的斑马鱼血管母细胞通过增强内皮细胞kdr的敏感性VEGF。
Endothelial cell-specific chemotaxis receptor (ECSCR) is a cell surface protein expressed by blood endothelial cells with roles in endothelial cell migration and signal transduction. We investigated the function of ecscr in the development of the zebrafish vasculature. Zebrafish ecscr is expressed in angioblasts and in axial vessels during angioblast migration and vasculogenesis. Morpholino-directed ecscr knockdown resulted in defective angioblast migration in the posterior lateral plate mesoderm, a process known to depend on vascular endothelial-derived growth factor (VEGF). In cultured cells, transfected ECSCR localized to actin-rich membrane protrusions, colocalizing with kinase insert domain protein receptor (KDR)/VEGF receptor 2 in these regions. ECSCR-silenced cells show reduced VEGF-induced phosphorylation of KDR but not of FMS-like tyrosine kinase 1 (FLT1)/VEGF receptor 1. Finally, chemical inhibition of VEGF receptor activity in zebrafish resulted in angioblast deficiencies that partially overlap with those seen in ecscr morphants. We propose that ecscr promotes migration of zebrafish angioblasts by enhancing endothelial kdr sensitivity to VEGF.