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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Andreone, BJ; Chow, BW; Tata, A; Lacoste, B; Ben-Zvi, A; Bullock, K; Deik, AA; Ginty, DD; Clish, CB; Gu, C

Published Date

  • May 3, 2017

Published In

Volume / Issue

  • 94 / 3

Start / End Page

  • 581 - 594.e5

PubMed ID

  • 28416077

Pubmed Central ID

  • PMC5474951

Electronic International Standard Serial Number (EISSN)

  • 1097-4199

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2017.03.043


  • eng

Conference Location

  • United States