Prohormone Convertases in Mouse Submandibular Gland: Co-localization of Furin and Nerve Growth FactorHooman Farhadi*,a, Sangeeta Pareek*,a, Robert Dayb, Weijia Dongb, Michel Chrétienb, John J. M. Bergeronc, Nabil G. Seidahb, and Richard A. Murphyaa Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada b J.A. DeSeve Laboratories of Biochemical and Molecular Endocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada c Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada Correspondence to: Richard A. Murphy, Montreal Neurological Institute, 3801 University Ave. Montreal QC H3A 2B4, Canada. Tel.: 514-398-5359; Fax: 514-398-8248. 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) Key Words: prohormone convertase, nerve growth factor, NGF, neurotrophins, PC1, PC2, furin, mouse submandibular glands, immunocytochemistry, in situ hybridization
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