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 |
| 巻 | 391 |
| 発行部数 | 1 |
| DOI | |
| 出版物ステータス | Published - 2010 1 1 |
| 外部発表 | Yes |
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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
}
TY - JOUR
T1 - Suppression of dynamin GTPase activity by sertraline leads to inhibition of dynamin-dependent endocytosis
AU - Takahashi, Kiyofumi
AU - Miyoshi, Hiroshi
AU - Otomo, Masahiro
AU - Osada, Kenichi
AU - Yamaguchi, Noboru
AU - Nakashima, Hideki
PY - 2010/1/1
Y1 - 2010/1/1
N2 - 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.
AB - 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.
KW - Dynamin
KW - Endocytosis
KW - GTPase
KW - Inhibitor
KW - Sertraline
UR - http://www.scopus.com/inward/record.url?scp=72949110366&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=72949110366&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2009.11.067
DO - 10.1016/j.bbrc.2009.11.067
M3 - Article
C2 - 19913505
AN - SCOPUS:72949110366
VL - 391
SP - 382
EP - 387
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -