Prohormone Convertases in Mouse Submandibular Gland: Co-localization of Furin and Nerve Growth Factor

Abstract

SUMMARY Nerve growth factor (NGF) in mouse submandibular glands (SGs) is generated from a 35-kD precursor by proteolytic enzymes that have yet to be identified. Prohormone convertases (PCs) cleave the NGF precursor in vitro, and in this study we questioned whether PCs could process salivary NGF in vivo. mRNA coding for PC2 (but not PC1) was detected on Northern blots of SG mRNA and also by in situ hybridization within parasympathetic neurons of intralobular ganglia. Northern blot and in situ hybridization analyses also detect mRNA coding for furin. In SGs of male mice, furin mRNA levels are high at birth and remain high throughout development. In glands from female mice, levels decline during postnatal development and are lower in adults than in newborns. Immunocytochemistry detects furin immunoreactivity in pro-acinar and ductal cells of glands from newborn and pubescent mice. In glands of adults, furin immunoreactivity is detectable in acinar cells but highest levels are present in NGF-containing granular convoluted tubule cells. These data, taken together with those from previous studies, suggest that furin is a candidate processing enzyme for NGF in mouse submandibular glands. (J Histochem Cytochem 45:795-804, 1997)

Nerve growth factor and proprotein convertases furin and PC7 in transected sciatic nerves and in nerve segments cultured in conditioned media: Their presence in Schwann cells, macrophages, and smooth muscle cells

“…Given this evidence and colocalization studies on serial sections (Fig. 11), we propose that furin and PC7 are likely to be convertases of NGF precursors expressed in these cells as has been suggested in other tissues (Meyer et al, 1996;Farhadi et al, 1997).…”

“…However, only a few studies have addressed the possible colocalization of PCs with neurotrophic factors in vivo. So far, furin and NGF have been colocalized by double in situ hybridization in the submaxillary gland (Meyer et al, 1996;Farhadi et al, 1997), whereas BDNF and PC1 were colocalized in the trigeminal ganglion (Meyer et al, 1996). Whether or not NGF and PCs colocalize in the injured sciatic nerve has not yet been demonstrated.…”

Nerve growth factor expression in parasympathetic neurons: regulation by sympathetic innervation

“…Our findings show that NGF mRNA is expressed within a majority of pterygopalatine neurons. Although NGF synthesis by these neurons has not been previously reported, the presence of mRNA encoding a prohormone convertase enzyme necessary for cleaving NGF from its precursor has been localized within parasympathetic neurons of the submandibular ganglion (Farhadi et al ., 1997). Together, these findings imply that parasympathetic neurons not only express mRNA necessary for NGF synthesis and immunoreactive protein, but also are capable of the post‐translational processing necessary to secrete biologically active NGF.…”

Characterization of nerve growth factor precursor protein expression by human prostate stromal cells: A role in selective neurotrophin stimulation of prostate epithelial cell growth

“…Prostate-specific antigen (PSA) and human kallikrein 2 (hK2), which possess chymotrypsin-like or trypsin-like activity, respectively, are both expressed in prostate tissue [28,29]. In addition, coexpression of the NGF precursor with several proprotein convertases, particularly furin, was shown to result in the secretion of processed NGF in vitro [30], leading to the suggestion that furin is a candidate processing enzyme for NGF [30,31]. Thus, the NGF precursor secreted by prostate stromal cells may be processed by enzymes other than those used in this study.…”