Developmental expression of a novel Kexin family protease, PACE4E, in the rat olfactory system

PACE4 is a mammalian Kexin family protease that is involved in the maturation of precursor proteins. Four PACE4 isoforms have been identified. We identified a novel PACE4 isoform, PACE4E, from a human cerebellum cDNA library, which possesses a hydrophobic cluster in its C-terminus participating in membrane association. The size of PACE4E mRNA from adult rat brain was estimated by Northern blotting to be 4.4 kb. In situ hybridization histochemistry revealed that the highest level of PACE4E mRNA was expressed in the mitral cells of the adult rat olfactory bulb (OB). The OB is a unique sensory organ in that it has a lifelong regenerating capacity and it affects brain development. We further analyzed the expression of PACE4E mRNA in the developing olfactory system. On day 13.5 of gestation, PACE4E mRNA was expressed at high levels in the neuroepithelium of the forebrain vesicle (FV), olfactory epithelium, and cells in the fiber bundles projecting to the FV. As development proceeded, PACE4E mRNA was expressed in developing mitral cells but decreased in the olfactory epithelium. In the newborn, its expression was confined to the mitral cells in both the main and accessory OB and in some periglomerular cells, as shown in adult rats. The spatio-temporal expression of PACE4E suggests that it plays a role in the establishment and maintenance of the olfactory receptor system.