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

研究成果: Article

14 引用 (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.

元の言語English
ページ(範囲)382-387
ページ数6
ジャーナルBiochemical and Biophysical Research Communications
391
発行部数1
DOI
出版物ステータスPublished - 2010 1 1
外部発表Yes

Fingerprint

Dynamin I
Dynamins
Sertraline
GTP Phosphohydrolases
Endocytosis
Dynamin II
Synaptic Vesicles
Phosphatidylserines
Cells
Guanosine Triphosphate
HeLa Cells
Serine
Cell Line
Serotonin Uptake Inhibitors
Neurology
Transferrin
Neuroblastoma
Liposomes
Nervous System
Neurotransmitter Agents

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

これを引用

Suppression of dynamin GTPase activity by sertraline leads to inhibition of dynamin-dependent endocytosis. / Takahashi, Kiyofumi; Miyoshi, Hiroshi; Otomo, Masahiro; Osada, Kenichi; Yamaguchi, Noboru; Nakashima, Hideki.

:: Biochemical and Biophysical Research Communications, 巻 391, 番号 1, 01.01.2010, p. 382-387.

研究成果: Article

Takahashi, Kiyofumi ; Miyoshi, Hiroshi ; Otomo, Masahiro ; Osada, Kenichi ; Yamaguchi, Noboru ; Nakashima, Hideki. / Suppression of dynamin GTPase activity by sertraline leads to inhibition of dynamin-dependent endocytosis. :: Biochemical and Biophysical Research Communications. 2010 ; 巻 391, 番号 1. pp. 382-387.
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