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

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)382-387
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume391
Issue number1
DOIs
Publication statusPublished - 2010 Jan 1
Externally publishedYes

Keywords

  • Dynamin
  • Endocytosis
  • GTPase
  • Inhibitor
  • Sertraline

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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