Suppression of dynamin GTPase activity by sertraline leads to inhibition of dynamin-dependent endocytosis

Kiyofumi Takahashi, Hiroshi Miyoshi*, Masahiro Otomo, Kenichi Osada, Noboru Yamaguchi, Hideki Nakashima

*この研究の対応する著者

研究成果査読

18 被引用数 (Scopus)

抄録

Dynamin (Dyn) 1 plays a role in recycling of synaptic vesicles, and thus in nervous system function. We previously showed that sertraline, a selective serotonin reuptake inhibitor (SSRI), is a mixed-type inhibitor of Dyn 1 with respect to both GTP and l-α-phosphatidyl-l-serine (PS) in vitro, and we suggested that it may regulate the neurotransmitter transport by modulating synaptic vesicle endocytosis via inhibition of Dyn 1 GTPase. Here, we investigated the effect of sertraline on endocytosis of marker proteins in human neuroblastoma SH-Sy5Y cells and HeLa cells. Sertraline inhibited endocytosis in both cell lines. Western blotting showed that SH-Sy5Y expresses Dyn 1 and Dyn 2, while HeLa expresses only Dyn 2. GTPase assay showed that sertraline inhibited Dyn 2 as well as Dyn 1. Therefore, the effect of sertraline on endocytosis was mediated by Dyn 2, at least in HeLa cells, as well as by Dyn 1 in cell lines that express it. Moreover, the inhibition mechanism of transferrin (Tf) uptake by sertraline differed from that in cells expressing Dyn 1 K44A, a GTP binding-defective variant, and sertraline did not interfere with the interaction between Dyn 1 and PS-liposomes.

本文言語English
ページ(範囲)382-387
ページ数6
ジャーナルBiochemical and Biophysical Research Communications
391
1
DOI
出版ステータスPublished - 2010 1 1
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 生物理学
  • 細胞生物学
  • 分子生物学

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