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Mechanisms of Participation of the Urokinase Receptor in Directed Axonal Growth

  • MOLECULAR CELL BIOLOGY
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Abstract

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 uPAR in 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.

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Funding

The study was financially supported by the Russian Foundation for Basic Research (project no. 17-04-00386).

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Authors and Affiliations

  1. Institute of Experimental Cardiology, National Cardiology Research Center, Ministry of Health of the Russian Federation, 121552, Moscow, Russia

    P. S. Klimovich & E. V. Semina

  2. Faculty of Fundamental Medicine, Lomonosov Moscow State University, 119991, Moscow, Russia

    P. S. Klimovich & E. V. Semina

Authors
  1. P. S. Klimovich
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  2. E. V. Semina
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Correspondence to E. V. Semina.

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All procedures performed in this work comply with the ethical standards of the institutional committee for research ethics and the 1964 Helsinki Declaration and its subsequent changes or comparable ethical standards.

Confict of interest. The authors declare they have no conflict of interest.

Additional information

Abbreviations: uPA, urokinase; uPAR, urokinase receptor; suPAR, soluble form of uPAR; GPI, glycosylphosphatidylinositol; ECM, extracellular matrix; DRG, dorsal root ganglion; CNS, central nervous system; IGF-1, insulin-like growth factor 1; GM-CMF, granulocyte macrophage colony stimulating factor; PT, pertussis toxin.

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Klimovich, P.S., Semina, E.V. Mechanisms of Participation of the Urokinase Receptor in Directed Axonal Growth. Mol Biol 54, 89–98 (2020). https://doi.org/10.1134/S0026893320010094

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