Lipoprotein lipase-mediated interactions of small proteoglycans and low-density lipoproteins.
According to numerous studies low-density lipoproteins (LDL) are supposed to interact with the glycosaminoglycan chain(s) of proteoglycans, e.g. with decorin and biglycan, which themselves are subject to receptor-mediated endocytosis. We tested, therefore, whether complexes of LDL and small proteoglycans can be endocytosed by either the LDL- or the small proteoglycan uptake mechanism. However, neither was the endocytosis of LDL significantly influenced by proteoglycans nor that of proteoglycans by LDL. This negative result could be explained by the observation that in vitro complex formation takes place only in buffers of low ionic strength. Under physiological conditions additional molecules may be necessary for complex stabilization. Lipoprotein lipase (LpL) which binds LDL was also able to interact with high affinity with decorin and its glycosaminoglycan-free core protein, both interactions being heparin-sensitive. Regardless of the presence or absence of LDL, LpL stimulated the endocytosis of decorin 1.5-fold, whereas LpL mediated a 4-fold stimulation of LDL uptake in the absence of decorin. No significant additional effect was seen in the presence of small concentrations of proteoglycans whereas in the presence of 1 microM decorin the endocytosis of [125I]LDL was reduced in normal as well as in LDL receptor-deficient fibroblasts. These observations could best be explained by assuming that LpL/LDL complexes are internalized upon binding to membrane-associated heparan sulphate and that small proteoglycans interfere with this process. It could not be ruled out, however, that a small proportion of the complexes is also taken up by the small proteoglycan receptor.
Schönherr
E
E
Institutes of Physiological Chemistry and Pathobiochemistry, University of Münster, Germany. schonhe@uni-muenster.de
Zhao
B
B
Hausser
H
H
Müller
M
M
Langer
C
C
Wagner
W D
WD
Goldberg
I J
IJ
Kresse
H
H
D058578:Biglycan; D002850:Chromatography, Gel; D058575:Decorin; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000493:pharmacokinetics; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism*
C546884:BGN protein, human; D058578:Biglycan; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D008077:Lipoproteins, LDL; D011509:Proteoglycans; D006493:Heparin; D008071:Lipoprotein Lipase