Plasminogen activators and their interaction with the extracellular matrix in neural development, plasticity and regeneration

Plasminogen activators are extracellular serine proteases, which are actively secreted by developing and regenerating neurons. These molecules, as discussed in this review, have been implicated in cell migration, axonal growth, growth factor activation, and synaptic remodeling associated with learning. Secreted plasminogen activators not only bind to their specific cell surface receptors, where they retain full proteolytic activity, but they also associate with extracellular matrix molecules including fibronectin and laminin. Plasminogen activator association with specific matrix proteins may target these proteins for degradation, altering the matrix composition and leading to intracellular signaling and influencing cell differentiation. The secreted plasminogen activators can bring about the degradation of matrix molecules either directly, or indirectly via the formation of plasmin.