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.
A New Function for the LDL Receptor: Transcytosis of LDL across the Blood–Brain Barrier
Please address all correspondence to Dr. Roméo Cecchelli, INSERM U325, Institut Pasteur, 590019 Lille Cédex, France. Tel.: (33) 3-20-87-73-81; Fax: (33) 3-20-8773-60; E-mail: [email protected]
This work was partly supported by a grant from the Association Recherche et Partage, by Institut National de la Santé et de la Recherche Médicale (INSERM U 325; Professor J.C. Fruchart), and by the Centre National de la Recherche Scientifique (UMR 111; Professor A. Verbert).
Bénédicte Dehouck, Laurence Fenart, Marie-Pierre Dehouck, Annick Pierce, Gérard Torpier, Roméo Cecchelli; A New Function for the LDL Receptor: Transcytosis of LDL across the Blood–Brain Barrier . J Cell Biol 25 August 1997; 138 (4): 877–889. doi: https://doi.org/10.1083/jcb.138.4.877
Download citation file:
Sign in
Client Account
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement
Advertisement