The synaptic proteins neurexins and neuroligins are widely expressed in the vascular system and contribute to its functions

The synaptic proteins neurexins and neuroligins are widely expressed in the vascular system and contribute to its functions
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DOI:
10.1073/pnas.0809510106
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发表时间:
2009-12-08
影响因子:
11.1
通讯作者:
Arese, Marco
Arese, Marco
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bottos, Alessia;Destro, Erika;Arese, Marco

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不像其他神经元的对应物,初级突触蛋白不知道参与血管生理。在这里,我们证明神经素和神经素构成了突触活动中庞大而复杂的基本参与者家族,它们是由整个血管系统中的内皮细胞和血管平滑肌细胞产生和加工的。此外,它们在血管重塑过程中受到动态调节,并在大血管和大脑中形成内源性复合物。我们使用鸡绒毛膜尿囊膜作为系统进行功能研究,并证明抗-神经素的单克隆重组抗体抑制血管生成,而外源性神经素则促进血管生成。最后,作为对-neurexin作用机制的深入研究,我们发现抗-neurexin抗体影响离体鸡动脉的血管张力。我们的发现有力地支持了这样一种观点,即即使是神经系统中发生的最复杂和最具可塑性的事件(即突触活动)也与血管系统共享分子线索。
Unlike other neuronal counterparts, primary synaptic proteins are not known to be involved in vascular physiology. Here, we demonstrate that neurexins and neuroligins, which constitute large and complex families of fundamental players in synaptic activity, are produced and processed by endothelial and vascular smooth muscle cells throughout the vasculature. Moreover, they are dynamically regulated during vessel remodeling and form endogenous complexes in large vessels as well as in the brain. We used the chicken chorioallantoic membrane as a system to pursue functional studies and demonstrate that a monoclonal recombinant antibody against beta-neurexin inhibits angiogenesis, whereas exogenous neuroligin has a role in promoting angiogenesis. Finally, as an insight into the mechanism of action of beta-neurexin, we show that the anti-beta-neurexin antibody influences vessel tone in isolated chicken arteries. Our finding strongly supports the idea that even the most complex and plastic events taking place in the nervous system (i.e., synaptic activity) share molecular cues with the vascular system.