Carboxypeptidase D is a potential candidate to carry out redundant processing functions of carboxypeptidase E based on comparative distribution studies in the rat central nervous system

Post-translational processing is essential for the biological activation of many proteins and peptides. After precursor cleavage at specific single re sidues or pairs of basic residues by the proprotein convertases, the C-term inal basic residues are removed. Carboxypeptidase E was thought to be the o nly enzyme responsible. Recent studies with carboxypeptidase E-deficient mi ce: Cpe(fat)/Cpe(fat), indicated the existence of carboxypeptidase E-like c arboxypeptidases. such as carboxypeptidase D. In order to define potential redundant functions in vivo, we compared the distributions of both carboxyp eptidases in the rat central nervous system and selected endocrine tissues. Carboxypeptidase D messenger RNA was abundantly expressed in glial cells i n the gay and white matter, while neurons in several brain regions, such as the piriform cortex, basolateral amygdala and hippocampus, also expressed high levels of carboxypeptidase D messenger RNA. Co-localization of carboxy peptidases E and D messenger RNAs was observed in many brain regions; the s pinal cord and endocrine tissues. Immunohistochemistry showed the intracell ular distribution of carboxypeptidase D with a perinuclear pattern. The ext ensive distribution of carboxypeptidase D in both glial and neuronal cells indicates the important role of carboxypeptidase D in peptide processing, p ossibly working together with furin, a ubiquitously expressed proprotein co nvertase. The co-localization of carboxypeptidases D and E suggests that carboxypepti dase D may, at least partially, compensate for carboxypeptidase E processin g functions in Cpe(fat)/Cpe(fat) mice. (C) 1999 IBRO. Published by Elsevier Science Ltd.