The C-Terminal Region of Serotonin Transporter Is Important for Its Trafficking and Glycosylation
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概要
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We investigated the effects of brefeldin A and ilimaquinone, inhibitors of membrane trafficking, using serotonin transporter (SERT)–expressing COS-7 cells. Both drugs significantly inhibited the serotonin uptake activity of SERT and caused SERT to be retained in the endoplasmic reticulum (ER), indicating that membrane trafficking is an important factor for SERT functional regulation. In agreement with previous reports, a C-terminal–deletion mutant of SERT (SERTΔCT) mostly localized to the ER and completely lacked serotonin uptake activity. To further elucidate the role of the C-terminus of SERT, we investigated whether overexpression of FLAG-tagged SERT C-terminus (FLAG-SERT-CT) affected the serotonin uptake activity and glycosylation of SERT. Interestingly, when concomitantly expressed with full-length FLAG-SERT in COS-7 cells, FLAG-SERT-CT increased the serotonin uptake activity and mature glycosylation of FLAG-SERT. These results indicate that the C-terminal region of SERT plays a crucial role in the functional regulation of SERT via membrane trafficking and glycosylation. In addition, proteasome inhibitors induced apparent ER stress, significantly decreased the serotonin uptake activity and mature glycosylation of SERT and caused SERT to be localized to the ER, suggesting that SERT function would be attenuated via membrane trafficking in pathological states that trigger ER stress.
- 2009-12-20
著者
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NOBUKUNI Mariko
Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hi
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MOCHIZUKI Hideki
Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Hiroshima U
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OKADA Satoshi
Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hi
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KAMEYAMA Nobuhisa
Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hi
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TANAKA Anna
Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hi
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YAMAMOTO Hikaru
Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hi
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AMANO Taku
Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hi
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SEKI Takahiro
Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hi
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SAKAI Norio
Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hi
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斎藤 尚亮
神戸大学・バイオシグナル研究センター
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斎藤 尚亮
神戸大、バイオシグナル研究センター
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Sakai Norio
Department Of Molecular And Pharmacological Neuroscience Graduate School Of Biomedical Sciences Hiro
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Yamamoto Hikaru
Depart Of Physics Kyoto University
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Yamamoto Hikaru
Dep. Of Molecular And Pharmacological Neuroscience Graduate School Of Biomedical Sciences Hiroshima
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Yamamoto Hikaru
Department Of Molecular And Pharmacological Neuroscience Graduate School Of Biomedical Sciences Hiro
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Nobukuni Mariko
Department Of Molecular And Pharmacological Neuroscience Graduate School Of Biomedical Sciences Hiro
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Seki T
Tokyo Inst. Technol. Yokohama
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Seki Takahiro
Department Of Molecular And Pharmacological Neuroscience Graduate School Of Biomedical Sciences Hiro
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Amano T
Department Of Molecular And Pharmacological Neuroscience Graduate School Of Biomedical Sciences Hiro
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Amano Taku
Department Of Pharamacology Hiroshima University School Of Medicine
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Tanaka Anna
Department Of Molecular And Pharmacological Neuroscience Graduate School Of Biomedical Sciences Hiro
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Seki T
Department Of Molecular And Pharmacological Neuroscience Graduate School Of Biomedical Sciences Hiro
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Seki Takahiro
Chemical Resources Laboratory Tokyo Institute Of Technology
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Seki Takahiro
Photofunctional Chemistry Division Research Laboratory Of Resources Utilization Tokyo Institute Of T
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Seki Takahiro
Department Of Molecular Pharmacology Faculty Of Pharmaceutical Sciences Kyoto University
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Serikawa T
Institute Of Laboratory Animals Kyoto University
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Serikawa Tadao
Inst. Of Lab. Animals Graduate School Of Medicine Kyoto Univ.
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Mukai Hideyuki
Department Of Ophthalmology And Visual Sciences Graduate School Of Biomedical Sciences Hiroshima Uni
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Amano Taku
Department Of Pharmacology Hiroshima University School Of Medicine
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斎藤 尚亮
神戸大学バイオシグナル研究センタｰ分子薬理分野
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Serikawa Tadao
信州大学医学部附属加齢適応研究センター
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Mochizuki Hideki
Department Of Neurology Juntendo University School Of Medicine
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Kameyama Nobuhisa
Department Of Molecular And Pharmacological Neuroscience Graduate School Of Biomedical Sciences Hiro
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Amano Taku
Department Of Molecular And Pharmacological Neuroscience Graduate School Of Biomedical Sciences Hiro
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関 隆広
Inst. Of Lab. Animals Graduate School Of Medicine Kyoto Univ.
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Seki T
Department Of Molecular Pharmacology Faculty Of Pharmaceutical Sciences Kyoto University
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Matsubayashi Hiroaki
Department Of Ophthalmology And Visual Sciences Graduate School Of Biomedical Sciences Hiroshima Uni
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Sakai Norio
Department Of Developmental Medicine (pediatrics) D-5 Osaka University Graduate School Of Medicine.
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Tanaka Anna
Department Of Molecular And Applied Bioscience Graduate School Of Biosphere Science Hiroshima Univer
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Seki Takahiro
Department Of Computer Science Tokyo Institute Of Technology:(present Address)ibm Global Service-jap
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Sakai Norio
Department Of Biopharmaceutics And Drug Rational Research Center School Of Pharmacy Tokyo University
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Okada Satoshi
Department Of Molecular And Pharmacological Neuroscience Graduate School Of Biomedical Sciences Hiro
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Okada Satoshi
Department Of Applied Chemistry And Biotechnology University Of Fukui
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Seki Takahiro
Department Of Molecular And Pharmacological Neuroscience Graduate School Of Biomedical Sciences Hiro
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Sakai Norio
Department Of Molecular And Pharmacological Neuroscience Graduate School Of Biomedical Sciences Hiro
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Seki Takahiro
Department Of Applied Physics Nagoya University
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Mochizuki Hideki
Department of Chemistry, Faculty of Science, Tokyo Metropolitan University
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