Immunohistochemical distribution of the prohormone convertase PC5-A in ratbrain

Prohormone convertase 5 is an endoprotease of the kexin/subtilisin-like fam ily, which has been postulated to play a role in the proteolytic maturation of a variety of pro-peptides in the mammalian brain. Ln order to gain insi ght into the functional role of prohormone convertase 5 in the central nerv ous system, the regional, cellular and subcellular distributions of the enz yme were investigated by immunohistochemistry in rat brain using an N-termi nal-directed specific antibody shown previously to recognize both the matur e and unprocessed forms of the enzyme. Throughout the brain, prohormone con vertase 5 immunoreactivity was concentrated within nerve cell bodies and pr oximal dendrites. No prohormone convertase 5 immunoreactivity was associate d with astrocytes, as confirmed by the absence of prohormone convertase 5 i mmunolabeling in cells immunopositive for the glial protein S-100 alpha. Wi thin neurons, prohormone convertase 5 immunoreactivity was concentrated wit hin the Golgi apparatus, as revealed immunohistochemically within the same sections using antibodies against the medial cisternae protein MG-160, It w as also present within small vesicular-like elements distributed throughout the cytoplasm of perikarya and dendrites, but not of axons, as confirmed b y its lack of co-localization with the synaptic terminal marker Dynamin-1. These results suggest that prohormone convertase 5 is active within early c ompartments of the neuronal regulated secretory pathway and that it is unli kely to be released with its processed substrates. Ar the regional level, p rohormone convertase 5-immunoreactive perikarya were distributed extensivel y throughout the forebrain. The most numerous and intensely labeled were de tected in the olfactory bulb, cerebral cortex, globus pallidus, endopeduncu lar and subthalamic nuclei, septum, diagonal band of Broca, magnocellular a nd medial preoptic areas, supraoptic and arcuate nuclei of the hypothalamus , and anterodorsal, laterodorsal, paraventricular and reticular nuclei of t he thalamus. Moderate to dense neuronal labeling was also evident in the ol factory tubercle, caudate-putamen, claustrum, bed nucleus of the stria term inalis, substantia innominata, hippocampus, amygdala, and remaining thalami c and hypothalamic nuclei. This widespread distribution suggests that prohormone convertase 5 is invol ved in the processing of a variety of neuropeptide and/or neurotrophin prec ursors in mammalian brain. (C) 1999 IBRO. Published by Elsevier Science Ltd .