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-alpha-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.
References
Jul 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·J HolmgrenL Svennerholm
Oct 1, 1981·British Journal of Clinical Pharmacology·M B YoudimB Oppenheim
Nov 1, 1994·The Journal of Cell Biology·H DamkeS L Schmid
Aug 1, 1993·The Journal of Cell Biology·A M van der BliekS L Schmid
Dec 1, 1993·The Journal of Cell Biology·L H WangR G Anderson
Aug 1, 1993·The Journal of Cell Biology·J S HerskovitsR B Vallee
Aug 18, 1997·FEBS Letters·H T McMahonC Smith
May 16, 1998·The Journal of Cell Biology·J R HenleyM A McNiven
Sep 3, 1998·Molecular Biology of the Cell·H CaoM A McNiven
Sep 18, 1999·Cell·W R Schafer
Feb 29, 2000·Journal of Neurochemistry·H H SitteE A Singer
Sep 13, 2001·Molecular Biology of the Cell·H DamkeT Baba
Jan 26, 2002·Molecular Biology of the Cell·Ellen M van Dam, Willem Stoorvogel
Jan 8, 2005·Science·Takayuki YamashitaTomoyuki Takahashi
Apr 19, 2005·The Journal of Biological Chemistry·Elena SolomahaH Clive Palfrey
Jun 15, 2005·Neuron·Wolf J JockuschLeon Lagnado
Dec 16, 2006·The EMBO Journal·Rajesh RamachandranSandra L Schmid
Apr 28, 2007·Science·Shawn M FergusonPietro De Camilli
Aug 19, 2007·Molecular Pharmacology·Annie QuanPhillip J Robinson
Oct 17, 2007·Structure·Jason A MearsJenny E Hinshaw
Aug 2, 2008·Biological & Pharmaceutical Bulletin·Masahiro OtomoNoboru Yamaguchi
Citations
Aug 16, 2012·Molecular Neurodegeneration·Masatoshi KonnoAtsushi Takeda
Mar 22, 2014·Nature Protocols·Mark J RobertsonAdam McCluskey
Feb 27, 2014·The Journal of Clinical Investigation·Alexis R Demonbreun, Elizabeth M McNally
Dec 12, 2012·Bioscience, Biotechnology, and Biochemistry·Kiyofumi TakahashiHiroshi Miyoshi
Dec 4, 2014·Neurobiology of Disease·Atsushi TsujimuraMasaki Tanaka
Jan 18, 2013·Movement Disorders : Official Journal of the Movement Disorder Society·Tetsutaro Ozawa
Feb 20, 2015·Traffic·James A DanielPhillip J Robinson
Aug 2, 2018·Biological Chemistry·Susanne Eschenburg, Thomas F Reubold
Nov 24, 2016·Molecular Pharmacology·Mahaveer SinghTanya Bhatt
Jul 26, 2014·The EMBO Journal·Liang WengMasahide Takahashi
Apr 14, 2017·Oncotarget·Jianghui Meng
May 20, 2020·The FEBS Journal·Oleg O Glebov
May 10, 2012·ACS Medicinal Chemistry Letters·Mark J RobertsonAdam McCluskey