Regional and cellular localization of the neuroendocrine prohormone convertases PC1 and PC2 in the rat central nervous system

PC1 and PC2 are two major enzymes involved in the processing of protein pre cursors directed to the regulated secretory pathway. Whereas transcripts en coding both enzymes are widely distributed in the central nervous system, i nformation regarding the localization of proteins themselves is still lacki ng. In an attempt to gain insight into the neurobiologic roles of PC1 and P C2, both enzymes were immunolocalized in the rat brain by using C-terminall y directed antibodies, which respectively recognize the 87-kDa PC1 and the 75 and 68-kDa PC2 forms. Adjacent sections immunoreacted with PCI or PC2 an tibodies exhibited selective patterns of immunostaining in regions well cha racterized with respect to their biosynthesis of multiple neuropeptides suc h as the cerebral cortex, hippocampus, and hypothalamus. PCI signal intensi ty was generally weaker than that of PC2, although both enzymes displayed e xtensive overlapping patterns of expression. As assessed by double-labeling experiments at the cellular level, PC1 and PC2 immunoreactive signals were localized within the trans-Golgi network and nerve terminals, in keeping w ith the biosynthetic pathways of neuropeptides. Immunoreactive fibers were detected in many areas throughout the brain but were particularly densely d istributed in the hypothalamus and the brainstem. Both enzymes were also lo calized within dendrites of numerous neurons, supporting the hypothesis tha t dendritic neuropeptide maturation and release may occur in a large number of brain regions. Taken together, our results provide new evidence that bo th convertases are efficiently targeted to the neuronal regulated secretory pathway and are well poised to process protein precursors in biologically active end-products within the mammalian brain. (C) 2099 Wiley-Liss, Inc.