Coexpression of proprotein convertase SPC3 and the neuroendocrine precursor proSAAS

The subtilisin-like proprotein convertases are a family of serine proteinases involved in the processing of secreted proteins via cleavage at paired basic residues. Until recently, only one natural inhibitor had been demonstrated, the neuropeptide 7B2, which contains a C-terminal domain with inhibitory activity against SPC2. A novel granin-like peptide precursor, named proSAAS, has recently been identified that contains potent and specific inhibitory activity on SPC3 in vitro. To exert such an inhibitory action of SPC3 activity, it would be important to demonstrate that proSAAS and SPC3 are colocalized. We have studied the expression of proSAAS and SPC3 mRNAs in the rat central nervous system and various peripheral tissues by in situ hybridization histochemistry. Our results show that, like 7B2, proSAAS is expressed with a panneuronal distribution. In the periphery, proSAAS is an excellent marker of endocrine cells. Double labeling studies show that SPC3 expression is nearly always accompanied by proSAAS expression. However, proSAAS was also found to be expressed in endocrine cells and neurons that did not express SPC3, suggesting that proSAAS could have additional functions other than the modulation of SPC3 activity. These data support the hypothesis that one of the roles of proSAAS may be to modulate the activity of SPC3.