AJP - Renal Physiology, Vol 253, Issue 4 648-F655, Copyright © 1987 by American Physiological Society
Presence and possible role of a renal brush-border Gly-Pro-X-releasing exopeptidase
K. J. Andersen and J. K. McDonald
Section for Clinical Research and Molecular Medicine, University of Bergen, Norway.
Differential pelleting of a rat renal cortical homogenate clearly
demonstrated the microsomal localization of an N-terminal exopeptidase of
the tripeptidyl peptidase (TPP) class that typically requires a free
N-terminus to catalyze the release of collagen-related (Gly-Pro-X)
"triplets" at pH 7.0 (TPP 7). Once fractionated by differential pelleting,
microsomal populations of different size were subfractionated by
equilibrium banding in sucrose gradients for the purpose of comparing the
distribution profiles and the isopycnic banding densities of TPP 7 to those
for known marker enzymes. This analytical approach permitted the
localization of these enzymes to specific membrane domains in the renal
cortex and provided evidence for the brush-border location of TPP 7.
Notably, dipeptidyl peptidase IV (DPP IV), an established plasma membrane
exopeptidase with a prolyl-bond specificity, gave banding densities and
distributions that were consistent with the presence of both TPP 7 and DPP
IV in the same membrane compartment. Because triplets of the Gly-Pro-X type
released by TPP 7 would be ideal substrates for DPP IV, a coupled TPP 7-DPP
IV exopeptidase mechanism at the luminal surface (brush border) of proximal
tubule cells could therefore make a major contribution to the renal
degradation and reabsorption of filtered collagen fragments.
