Regulation of Mct1 by cAMP-dependent internalization in rat brain endothelial cells

Jeffrey P. Smith, Amy L. Uhernik, Lun Li, Zejian Liu, Lester R Drewes

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


In the cerebrovascular endothelium, monocarboxylic acid transporter 1 (Mct1) controls blood-brain transport of short chain monocarboxylic and keto acids, including pyruvate and lactate, to support brain energy metabolism. Mct1 function is acutely decreased in rat brain cerebrovascular endothelial cells by β-adrenergic signaling through cyclic adenosine monophosphate (cAMP); however, the mechanism for this acute reduction in transport capacity is unknown. In this report, we demonstrate that cAMP induces the dephosphorylation and internalization of Mct1 from the plasma membrane into caveolae and early endosomes in the RBE4 rat brain cerebrovascular endothelial cell line. Additionally, we provide evidence that Mct1 constitutively cycles through clathrin vesicles and recycling endosomes in a pathway that is not dependent upon cAMP signaling in these cells. Our results are important because they show for the first time the regulated and unregulated vesicular trafficking of Mct1 in cerebrovascular endothelial cells; processes which have significance for better understanding normal brain energy metabolism, and the etiology and potential therapeutic approaches to treating brain diseases, such as stroke, in which lactic acidosis is a key component.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalBrain Research
StatePublished - Oct 22 2012

Bibliographical note

Funding Information:
The expert technical assistance of Ms. Mary Sneve is greatly appreciated. This research was funded by American Heart Association grant 0855638G , and National Institutes of Health, National Institute of Neurological Disorders and Stroke , grant 1R15NS062404-01A2 .


  • Blood-brain barrier
  • Caveolae
  • Cerebrovascular endothelium
  • Endocytosis
  • Monocarboxylic acid transporter
  • Regulation


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