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

Benjamin J. Andreone, Brian Wai Chow, Aleksandra Tata, Baptiste Lacoste, Ayal Ben-Zvi, Kevin Bullock, Amy A. Deik, David D. Ginty, Clary B. Clish, Chenghua Gu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

352 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)581-594.e5
JournalNeuron
Volume94
Issue number3
DOIs
StatePublished - 3 May 2017

Bibliographical note

Publisher Copyright:
© 2017 Elsevier Inc.

Keywords

  • CNS endothelial cells
  • Cav-1
  • DHA
  • Mfsd2a
  • blood vessels
  • blood-brain barrier
  • caveolae
  • lipid transport
  • lipidomic mass spectrometry
  • transcytosis

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