TY - JOUR
T1 - 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
AU - Dong, W.
AU - Fricker, L. D.
AU - Day, R.
N1 - Funding Information:
This work was supported by the Medical Research Council of Canada (MT14194 and MT13196 to R.D.). R.D. is a scholar (chercheur-boursier; Junior II) of the Fonds de la Recherche en Santé du Quebec (FRSQ).
PY - 1999
Y1 - 1999
N2 - Post-translational processing is essential for the biological activation of many proteins and peptides. After precursor cleavage at specific single residues or pairs of basic residues by the proprotein convertases, the C- terminal basic residues are removed. Carboxypeptidase E was thought to be the only enzyme responsible. Recent studies with carboxypeptidase E-deficient mice, Cpe(fat)/Cpe(fat), indicated the existence of carboxypeptidase E-like carboxypeptidases, such as carboxypeptidase D. In order to define potential redundant functions in vivo, we compared the distributions of both carboxypeptidases in the rat central nervous system and selected endocrine tissues. Carboxypeptidase D messenger RNA was abundantly expressed in glial cells in the gray 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 carboxypeptidases E and D messenger RNAs was observed in many brain regions, the spinal cord and endocrine tissues. Immunohistochemistry showed the intracellular distribution of carboxypeptidase D with a perinuclear pattern. The extensive distribution of carboxypeptidase D in both glial and neuronal cells indicates the important role of carboxypeptidase D in peptide processing, possibly working together with furin, a ubiquitously expressed proprotein convertase. The co-localization of carboxypeptidases D and E suggests that carboxypeptidase D may, at least partially, compensate for carboxypeptidase E processing functions in Cper(fat)/Cpe(fat) mice.
AB - Post-translational processing is essential for the biological activation of many proteins and peptides. After precursor cleavage at specific single residues or pairs of basic residues by the proprotein convertases, the C- terminal basic residues are removed. Carboxypeptidase E was thought to be the only enzyme responsible. Recent studies with carboxypeptidase E-deficient mice, Cpe(fat)/Cpe(fat), indicated the existence of carboxypeptidase E-like carboxypeptidases, such as carboxypeptidase D. In order to define potential redundant functions in vivo, we compared the distributions of both carboxypeptidases in the rat central nervous system and selected endocrine tissues. Carboxypeptidase D messenger RNA was abundantly expressed in glial cells in the gray 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 carboxypeptidases E and D messenger RNAs was observed in many brain regions, the spinal cord and endocrine tissues. Immunohistochemistry showed the intracellular distribution of carboxypeptidase D with a perinuclear pattern. The extensive distribution of carboxypeptidase D in both glial and neuronal cells indicates the important role of carboxypeptidase D in peptide processing, possibly working together with furin, a ubiquitously expressed proprotein convertase. The co-localization of carboxypeptidases D and E suggests that carboxypeptidase D may, at least partially, compensate for carboxypeptidase E processing functions in Cper(fat)/Cpe(fat) mice.
KW - Central nervous system
KW - Immunohistochemistry
KW - In situ hybridization
KW - Neuropeptides
KW - Processing
KW - Proprotein convertase
UR - http://www.scopus.com/inward/record.url?scp=0032977203&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032977203&partnerID=8YFLogxK
U2 - 10.1016/S0306-4522(98)00381-9
DO - 10.1016/S0306-4522(98)00381-9
M3 - Article
C2 - 10362316
AN - SCOPUS:0032977203
SN - 0306-4522
VL - 89
SP - 1301
EP - 1317
JO - Neuroscience
JF - Neuroscience
IS - 4
ER -