Implications of the subtilisin/kexin-like precursor convertases in the development and function of nervous tissues.

Furin, PC1, PC2, and PC5 represent mammalian convertases (PCs) found in endocrine, central and peripheral nervous tissues, which cleave a number of precursors at basic residues normally processed in vivo. Typical bonds cleaved by PCs include the pairs Lys-Arg, Arg-Arg and Arg-X-Lys/Arg-Arg. These cleavage sites have been detected following coexpression of each convertase in cell lines together with different precursors as models, including proopiomelanocortin (POMC), proinsulin and proNGF and proBDNF. The presence of PCs and different precursors was revealed by in situ hybridization or immunocytochemistry in cultured AtT-20 cells, in the developing CNS, pituitary, and pancreatic islets. In an experimental model of epilepsy in which epileptiform activities were provoked by kainic acid administration, we observed a similar transient expression of furin and PC1 as compared to that of NGF and BDNF. In conclusion, it is proposed that under different stimuli various precursors are activated by a unique cocktail of convertases, each of which either alone or in combination with others acts to process inactive precursors, and thereby playing an important role in development and in the plasticity of the neuronal system.