Identification of a receptor necessary for Nogo-B stimulated chemotaxis and morphogenesis of endothelial cells

Identification of a receptor necessary for Nogo-B stimulated chemotaxis and morphogenesis of endothelial cells
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DOI:
10.1073/pnas.0602427103
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发表时间:
2006-07-18
影响因子:
11.1
通讯作者:
Sessa, William C.
Sessa, William C.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Miao, Robert Qing;Gao, Yuan;Sessa, William C.

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Nogo亚型(Nogo-A和-B)参与调节神经和心血管功能,如细胞扩散和趋化性。与在所有Nogo亚型中发现的可以与神经特异性Nogo-66受体相互作用的环结构域(Nogo-66)不同,介导血管功能的Nogo-B的氨基末端的受体是未知的。在这里,我们确定了一个以前未表征的Nogo-B受体特异性Nogo-B的氨基末端,并表明Nogo-B受体定位与配体Nogo-B在VEGF和伤口愈合血管生成在体内,介导的趋化性在异源表达系统和趋化性,并在天然内皮细胞的三维管形成。因此,该受体的鉴定可能导致发现该途径的激动剂或拮抗剂以调节血管重塑和血管生成。
Nogo isoforms (Nogo-A and -B) have been implicated in regulating neural and cardiovascular functions, such as cell spreading and chemotaxis. Unlike the loop domain (Nogo-66) found in all Nogo isoforms that can interact with a neural-specific Nogo-66 receptor, the receptor for the amino terminus of Nogo-B that mediates vascular function is unknown. Here, we identify a previously uncharacterized Nogo-B receptor specificforthe amino terminus of Nogo-B and show that Nogo-B receptor localizes with the ligand Nogo-B during VEGF and wound healing angiogenesis in vivo, mediates chemotaxis in a heterologous expression system and chemotaxis, and 3D tube formation in native endothelial cells. Thus, identification of this receptor may lead to the discovery of agonists or antagonists of this pathway to regulate vascular remodeling and angiogenesis.