Mechanisms of Regulation of the Targeted Grown of Nerves and Vessels by Components of the Fibrinolytic System and GPI-Anchored Navigation Receptors

The targeted growth of nerves and vessels is controlled by navigation receptors, some of which are proteins with glycosylphosphatidylinositide “anchors.” Using T-cadherin and the urokinase receptor as examples, this review addresses the main molecular mechanisms of this process. T-cadherin functions as a navigation molecule negatively regulating the growth of axons and blood vessels. This substance is involved in regulating physiological and tumor neoangiogenesis. These effects are based on homophilic interactions between T-cadherin molecules and contacting cells. T-cadherin is also a receptor for low-density lipoproteins and adiponectin. The competition between these ligands seen in our studies at the level of T-cadherin-dependent intracellular signaling may constitute a new regulatory mechanism. Apart from the already known ability of the urokinase system (urokinase and its receptor and inhibitors) to stimulate cell migration, to carry out limited proteolysis of the extracellular matrix, and drive vessel growth and remodeling processes, this review presents data on its role in axon growth and branching and the recovery of nerves after damage. Data in recent years have provided evidence of the ability of the urokinase receptor to interact with other ligands. This interaction has great physiological significance for the formation and functioning of nervous system structures in health and pathology.