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A New Function for the LDL Receptor: Transcytosis of LDL across the Blood–Brain Barrier

Dehouck, Bénédicte, Fenart, Laurence, Dehouck, Marie-Pierre, Pierce, Annick, Torpier, Gérard, Cecchelli, Roméo·1997·The Journal of Cell Biology
DOI 10.1083/jcb.138.4.877PMC PMC2138047
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Abstract

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.

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  • Blood-circulating LDL molecules can cross the blood-brain barrier in a process mediated by the LDLR expressed in caveolin- or clathrin-coated vesicles in specialized BBB-endothelial cells.

    “Blood-circulating LDL molecules can also cross the BBB in a process mediated by the LDLR expressed in caveolin-or clathrin-coated vesicles in specialized BBB-endothelial cells.22”

    From Canonical Wnt pathway and the LDL receptor superfamily in neuronal cholesterol homeostasis and function (2024) · cites this paper as [22]

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Metadata

Authors
Dehouck, B., Fenart, L., Dehouck, M.-P., Pierce, A., Torpier, G., & Cecchelli, R.
Affiliations
*Institut National de la Santé et de la Recherche Médicale U325, Department of Atherosclerosis Institut Pasteur, 59000 Lille, France; and ‡Laboratoire de Chimie biologique (UMR 111), Université des Sciences et Technologies de Lille I, 59655 Villeneuve d'Ascq Cédex, France
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
1997-08-25
Volume
138
Issue
4
Pages
877-889
ISSN
  • 0021-9525
  • 1540-8140
DOI
10.1083/jcb.138.4.877
PMC
PMC2138047
Cited by
490
References
2
Language
en

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