Interaction of apo e-containing lipoproteins with the ldl receptor
-related protein, lrp.
K[umlaut]uchenhoff, Andreas, B[umlaut]arbel Harrach-Ruprecht, and
Horst Robenek.
Institute for Arteriosclerosis Research at the University of
M[umlaut]unster, Domagkstrasse 3, 48149 M[umlaut]unster, FRG
APStracts 3:0280C, 1996.
The low density lipoprotein receptor-related protein (LRP) is a
multifunctional cell surface receptor that interacts with
apolipoprotein (apo) E-rich lipoproteins, and 2-macroglobulin (2-M)
in the activated state (2-M*). Whether LRP is a physiologically
relevant lipoprotein receptor for naturally occurring apo E-rich
lipoproteins, however, is still under discussion. To address this
question we isolated -VLDL from rabbits by using gel filtration
chromatography. Biochemical analysis of -VLDL subfractions
demonstrated that we isolated apo E- and cholesterol-rich
triglycerides with differences in composition and size. Binding and
uptake characteristics of -VLDL subfractions and 2-M* on mouse
peritoneal macrophages (MPM) and Hep G2 cells were examined by
electron microscopy. One of the -VLDL subfractions, -VLDLII, bound
specifically to LRP on MPM and Hep G2. -VLDLII competed with the
binding of 2-M* without addition of exogenous apo E. Furthermore,
binding and uptake of -VLDLII and 2-M* was not affected by either
lactoferrin or Ca2+ free medium. The results indicate that naturally
occurring apo E-rich lipoproteins do exist and that they very likely
interact with LRP via the same binding site as 2-M*.
Received 6 May 1996; accepted in final form 23 August 1996.
APS Manuscript Number C239-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996