Lipoprotein lipase-mediated interactions of small proteoglycans and low-density lipoproteins

According to numerous studies low-density lipoproteins (LDL) are supposed t o interact with the glycosaminoglycan chain(s) of proteoglycans, e.g. with decorin and biglycan which themselves are subject to receptor-mediated endo cytosis. We tested, therefore, whether complexes of LDL and small proteogly cans can be endocytosed by either the LDL- or the small proteoglycan uptake mechanism, However, neither was the endocytosis of LDL significantly influ enced by proteoglycans nor that of proteoglycans by LDL. This negative resu lt could be explained by the observation that in vitro complex formation ta kes place only in buffers of low ionic strength, Under physiological condit ions additional molecules may be necessary for complex stabilization. Lipop rotein lipase (LpL) which binds LDL was also able to interact with high aff inity with decorin and its glycosaminoglycan-free core protein, both intera ctions being heparin-sensitive, Regardless of the presence or absence of LD L, 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 significa nt additional effect was seen in the presence of small concentrations of pr oteoglycans whereas in the presence of 1 muM decorin the endocytosis of [I- 125]LDL was reduced in normal as well as in LDL receptor-deficient fibrobla sts. These observations could best be explained by assuming that LpL/DL com plexes are internalized upon binding to membrane-associated heparan sulphat e 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.