Klimovich P S, Semina E V
Institute of Experimental Cardiology, National Cardiology Research Center, Ministry of Health of the Russian Federation, Moscow, 121552 Russia.
Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow, 119991 Russia.
Mol Biol (Mosk). 2020 Jan-Feb;54(1):103-113. doi: 10.31857/S0026898420010097.
The degradation of the extracellular matrix plays an important role in the processes of morphogenesis, angio- and neurogenesis, wound healing, inflammation, carcinogenesis and others. The urokinase receptor uPAR is an important participant in processes that regulate extracellular proteolysis, cell adhesion to the extracellular matrix, cell migration along the chemokine gradient, proliferation and survival involving growth factor receptors. The presence of the GPI anchor and the absence of transmembrane and cytoplasmic domains in uPAR promote involvement of membrane partners for the realization of uPAR signal effects. In some studies, involvement of the fMLP chemokine receptor FPRL in the regulation of uPAR-dependent directed migration has been shown. Moreover, the migration of neural progenitors and their maturation into neurons during the formation of brain structures are regulated by chemokine receptors. Despite the data on the role of uPARin the processes of morphogenesis, little is known about the interactions between uPAR and chemokine receptors in guidance processes during nerve growth and regeneration. In the present work, it was shown for the first time that the soluble form of uPAR (suPAR) regulates the trajectory of axon outgrowth, and this effect does not depend on the presence of urokinase. It was also shown that regulation of the directed axon growth is based on the interaction of suPAR with the chemokine receptor FPRL1. These data show new mechanisms for the participation of the urokinase system in the regulation of axon guidance.
细胞外基质的降解在形态发生、血管生成、神经发生、伤口愈合、炎症、致癌作用等过程中发挥着重要作用。尿激酶受体uPAR是调节细胞外蛋白水解、细胞与细胞外基质黏附、细胞沿趋化因子梯度迁移、涉及生长因子受体的增殖和存活等过程的重要参与者。uPAR中糖基磷脂酰肌醇（GPI）锚的存在以及跨膜和胞质结构域的缺失促进了膜伴侣参与uPAR信号效应的实现。在一些研究中，已表明fMLP趋化因子受体FPRL参与了uPAR依赖性定向迁移的调节。此外，在脑结构形成过程中，神经祖细胞的迁移及其向神经元的成熟受趋化因子受体的调节。尽管有关于uPAR在形态发生过程中作用的数据，但对于uPAR与趋化因子受体在神经生长和再生的导向过程中的相互作用知之甚少。在本研究中，首次表明可溶性uPAR（suPAR）调节轴突生长轨迹，且这种效应不依赖于尿激酶的存在。还表明定向轴突生长的调节基于suPAR与趋化因子受体FPRL1的相互作用。这些数据揭示了尿激酶系统参与轴突导向调节的新机制。
