Blood-Brain Barrier Permeability Is Regulated by Lipid Transport-Dependent Suppression of Caveolae-Mediated Transcytosis.

Autor:	Andreone BJ; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Chow BW; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Tata A; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Lacoste B; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Ben-Zvi A; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA., Bullock K; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Deik AA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Ginty DD; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA., Clish CB; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Gu C; Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA. Electronic address: chenghua_gu@hms.harvard.edu.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2017 May 03; Vol. 94 (3), pp. 581-594.e5. Date of Electronic Publication: 2017 Apr 13.
DOI:	10.1016/j.neuron.2017.03.043
Abstrakt:	The blood-brain barrier (BBB) provides a constant homeostatic brain environment that is essential for proper neural function. An unusually low rate of vesicular transport (transcytosis) has been identified as one of the two unique properties of CNS endothelial cells, relative to peripheral endothelial cells, that maintain the restrictive quality of the BBB. However, it is not known how this low rate of transcytosis is achieved. Here we provide a mechanism whereby the regulation of CNS endothelial cell lipid composition specifically inhibits the caveolae-mediated transcytotic route readily used in the periphery. An unbiased lipidomic analysis reveals significant differences in endothelial cell lipid signatures from the CNS and periphery, which underlie a suppression of caveolae vesicle formation and trafficking in brain endothelial cells. Furthermore, lipids transported by Mfsd2a establish a unique lipid environment that inhibits caveolae vesicle formation in CNS endothelial cells to suppress transcytosis and ensure BBB integrity. (Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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