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* Institut National de la Santé et de la Recherche Médicale U325, Department of Atherosclerosis Institut Pasteur, 59000 Lille,
France; and Lipoprotein transport across the blood-brain
barrier (BBB) is of critical importance for the delivery
of essential lipids to the brain cells. The occurrence of a
low density lipoprotein (LDL) receptor on the BBB
has recently been demonstrated. To examine further
the function of this receptor, we have shown using an in
vitro model of the BBB, that in contrast to acetylated
LDL, which does not cross the BBB, LDL is specifically transcytosed across the monolayer. The C7 monoclonal antibody, known to interact with the LDL receptor-binding domain, totally blocked the transcytosis of
LDL, suggesting that the transcytosis is mediated by
the receptor. Furthermore, we have shown that cholesterol-depleted astrocytes upregulate the expression of
the LDL receptor at the BBB. Under these conditions,
we observed that the LDL transcytosis parallels the increase in the LDL receptor, indicating once more that
the LDL is transcytosed by a receptor-mediated mechanism. The nondegradation of the LDL during the
transcytosis indicates that the transcytotic pathway in
brain capillary endothelial cells is different from the
LDL receptor classical pathway. The switch between a
recycling receptor to a transcytotic receptor cannot be
explained by a modification of the internalization signals of the cytoplasmic domain of the receptor, since we
have shown that LDL receptor messengers in growing
brain capillary ECs (recycling LDL receptor) or differentiated cells (transcytotic receptor) are 100% identical, but we cannot exclude posttranslational modifications of the cytoplasmic domain, as demonstrated for
the polymeric immunoglobulin receptor. Preliminary studies suggest that caveolae are likely to be involved in
the potential transport of LDL from the blood to the
brain.
Laboratoire de Chimie biologique (UMR 111), Université des Sciences et Technologies de Lille I, 59655 Villeneuve
d'Ascq Cédex, France
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