CELLULAR PROCESSING OF THE NEUROTROPHIN PRECURSORS OF NT3 AND BDNF BYTHE MAMMALIAN PROPROTEIN CONVERTASES

In order to define the enzymes responsible for the maturation of the p recursors of brain-derived neurotrophic factor (proBDNF) and neurotrop hin-3 (proNT3), we have analysed their biosynthesis and intracellular processing by the proprotein convertases furin, PC1, PC2, PACE4, PC5 a nd its isoform PC5/6-B. In these studies, we utilized a vaccinia virus expression system in either BSC40 or the furin activity-deficient LoV o cells, Results demonstrated that in both cells furin and, to a lesse r extent, PACE4 and PC5/6-B effectively process proBDNF and proNT3. Fu rthermore, pie have determined that human proNT3 is sulfated, suggesti ng that processing of proNT3 occurs following the arrival of the precu rsor to the Trans Golgi Network.