Distinct roles of ezrin, radixin and moesin in maintaining the plasma membrane localizations and functions of human blood–brain barrier transporters

Yutaro Hoshi, Yasuo Uchida, Takashi Kuroda, Masanori Tachikawa, Pierre Olivier Couraud, Takashi Suzuki, Tetsuya Terasaki

研究成果: Article査読

11 被引用数 (Scopus)

抄録

The purpose of this study was to clarify the roles of ERM proteins (ezrin/radixin/moesin) in the regulation of membrane localization and transport activity of transporters at the human blood–brain barrier (BBB). Ezrin or moesin knockdown in a human in vitro BBB model cell line (hCMEC/D3) reduced both BCRP and GLUT1 protein expression levels on the plasma membrane. Radixin knockdown reduced not only BCRP and GLUT1, but also P-gp membrane expression. These results indicate that P-gp, BCRP and GLUT1 proteins are maintained on the plasma membrane via different ERM proteins. Furthermore, moesin knockdown caused the largest decrease of P-gp and BCRP efflux activity among the ERM proteins, whereas GLUT1 influx activity was similarly reduced by knockdown of each ERM protein. To investigate how moesin knockdown reduced P-gp efflux activity without loss of P-gp from the plasma membrane, we examined the role of PKCβI. PKCβI increased P-gp phosphorylation and reduced P-gp efflux activity. Radixin and moesin proteins were detected in isolated human brain capillaries, and their protein abundances were within a 3-fold range, compared with those in hCMEC/D3 cell line. These findings may mean that ezrin, radixin and moesin maintain the functions of different transporters in different ways at the human BBB.

本文言語English
ページ(範囲)1533-1545
ページ数13
ジャーナルJournal of Cerebral Blood Flow and Metabolism
40
7
DOI
出版ステータスPublished - 2020 7 1

ASJC Scopus subject areas

  • 神経学
  • 臨床神経学
  • 循環器および心血管医学

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