Gene expression of prohormone and proprotein convertases in the rat CNS: a comparative in situ hybridization analysis.
Posttranslational processing of proproteins and prohormones is an essential step in the formation of bioactive peptides, which is of particular importance in the nervous system. Following a long search for the enzymes responsible for protein precursor cleavage, a family of Kexin/subtilisin-like convertases known as PC1, PC2, and furin have recently been characterized in mammalian species. Their presence in endocrine and neuroendocrine tissues has been demonstrated. This study examines the mRNA distribution of these convertases in the rat CNS and compares their expression with the previously characterized processing enzymes carboxypeptidase E (CPE) and peptidylglycine alpha-amidating monooxygenase (PAM) using in situ hybridization histochemistry. Furin mRNA was ubiquitously distributed and detected both in neurons and non-neuronal tissue throughout the brain with a higher abundance in ependyma, the circumventricular organs, the islands of Calleja, hippocampus, and allocortex. The cellular localization of PC1 and PC2 was exclusively neuronal with highest concentrations in known neuropeptide-rich brain regions. In general, PC2 was more widely expressed than PC1 in the CNS, although many regional variations were detected. The identification of specific combinations of convertase expression together with CPE and PAM expression in neuropeptide-rich brain regions suggests that specific enzymatic pathways are involved in neuropeptide precursor processing, and that these specific combinations are responsible for region-specific differences of posttranslational processing.
Schäfer
M K
MK
Mental Health Research Institute, University of Michigan, Ann Arbor 48109-0720.
Day
R
R
Cullinan
W E
WE
Chrétien
M
M
Seidah
N G
NG
Watson
S J
SJ
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000166:cytology / Q000201:enzymology*; D043423:Carboxypeptidase H; D002268:Carboxypeptidases / Q000235:genetics; D003001:Cloning, Molecular; D045683:Furin; D015870:Gene Expression; D017403:In Situ Hybridization; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics; D009097:Multienzyme Complexes; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D045706:Proprotein Convertase 2; D043484:Proprotein Convertases; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases / Q000235:genetics*; D013381:Subtilisins / Q000235:genetics*; D013462:Sulfur Radioisotopes; D014158:Transcription, Genetic
D009097:Multienzyme Complexes; D015347:RNA Probes; D012333:RNA, Messenger; D013462:Sulfur Radioisotopes; D006899:Mixed Function Oxygenases; C035189:peptidylglycine monooxygenase; D002268:Carboxypeptidases; D043423:Carboxypeptidase H; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D013381:Subtilisins; D045683:Furin; D045706:Proprotein Convertase 2