S. Takahashi et al., ENHANCEMENT OF THE BINDING OF TRIGLYCERIDE-RICH LIPOPROTEINS TO THE VERY-LOW-DENSITY LIPOPROTEIN RECEPTOR BY APOLIPOPROTEIN-E AND LIPOPROTEIN-LIPASE, The Journal of biological chemistry, 270(26), 1995, pp. 15747-15754
The low density lipoprotein (LDL) receptor plays a crucial role in cho
lesterol metabolism, A related protein, designated the very low densit
y lipoprotein (VLDL) receptor, that specifically binds apolipoprotein
(ape) E has recently been characterized and shown to be expressed in h
eart, muscle and adipose tissue and the human monocyte-macrophage cell
line THP-1, The VLDL receptor binds and internalizes VLDL and interme
diate density lipoprotein from Watanabe heritable hyperlipidemic (WHHL
) rabbits as well as beta-migrating VLDL from cholesterol-fed rabbits
but not LDL from WHHL rabbits, Chinese hamster ovary (CHO) cells trans
fected with the rabbit VLDL receptor cDNA have now been shown to bind
or internalize VLDL (d < 1.006 g/ml) isolated from fasted normolipidem
ic human subjects with lower affinity than WHHL-VLDL or rabbit beta-VL
DL, However, binding and internalization were markedly enhanced when f
asted human VLDL was preincubated with either recombinant human apoE (
3/3) or lipoprotein lipase (LPL) in CHO cells overexpressing the rabbi
t or human VLDL receptor, CHO cells transfected with both the rabbit V
LDL receptor cDNA and the human LPL cDNA effectively bound, internaliz
ed, and degraded fasted human VLDL without pretreatment. Treatment of
heparinase reduced the effect of LPL-mediated binding at 4 degrees C,
but the inhibitory effect was lower at 37 degrees C, Pseudomonas LPL a
lso enhanced the binding of human fasted VLDL to the VLDL receptor at
37 degrees C in CHO cells overexpressing the human VLDL receptor, Take
n together, LPL causes the enhancement of triglyceride-rich lipoprotei
ns binding to the VLDL receptor via both the formation of bridge betwe
en lipoproteins and heparan sulfate proteoglycans and its lipolytic ef
fect, Ligand blot analysis showed that the apparent molecular mass of
the VLDL receptor is 118 kDa, which is smaller than that of the LDL re
ceptor, These results indicate that the VLDL receptor recognizes both
triglyceride-rich lipoproteins that are also relatively rich in apoE,
as well as the remnants of triglyceride-rich lipoproteins after catabo
lism and the interaction with heparan sulfate proteoglycans by LPL, Th
e VLDL receptor may thus function as a receptor for remnants of trigly
ceride-rich lipoproteins in extrahepatic tissues.