Deficiency of Rab26 causes behavioral defects in mice through impaired trafficking of serotonin (5-HT) transporter
Summary: Rab proteins are key regulators of membrane trafficking. Dysregulated Rab proteins are associated with neurological diseases through the regulation of receptor endocytosis, recycling, and/or degradation. Rab26 is highly expressed in the brain, but its physiological function remains poorly e...
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Elsevier
2025-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225011927 |
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| author | Yandan Ren Ziyan Wang Ziheng Wei Ruijuan Zhuang Yongtao Zhang Xiaoxi Liu Cong Jiang Xuan Liu Ye Yun Yanfang Li Wanjin Hong Tuanlao Wang |
| author_facet | Yandan Ren Ziyan Wang Ziheng Wei Ruijuan Zhuang Yongtao Zhang Xiaoxi Liu Cong Jiang Xuan Liu Ye Yun Yanfang Li Wanjin Hong Tuanlao Wang |
| author_sort | Yandan Ren |
| collection | DOAJ |
| description | Summary: Rab proteins are key regulators of membrane trafficking. Dysregulated Rab proteins are associated with neurological diseases through the regulation of receptor endocytosis, recycling, and/or degradation. Rab26 is highly expressed in the brain, but its physiological function remains poorly elucidated. Here we demonstrate that Rab26 deficiency in mice causes depression and anxiety-like behaviors and cognitive impairment. The depletion of Rab26 results in the accumulation of synaptic vesicles in the presynaptic terminals and a decrease in the frequency of miniature excitatory postsynaptic currents (mEPSCs) and long-term potentiation (LTP). Mechanistically, Rab26 regulates the trafficking of serotonin (5-HT) transporter (SERT/Slc6a4). Rab26 interacts with SERT and promotes the autophagic degradation of SERT. Loss of Rab26 results in increased cell surface levels of SERT, suggesting that Rab26 plays a role in regulating the trafficking of SERT to maintain normal serotonin-mediated neurotransmission. |
| format | Article |
| id | doaj-art-86c485b5bdab430cbccc052f5c8cd1eb |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-86c485b5bdab430cbccc052f5c8cd1eb2025-08-20T03:31:06ZengElsevieriScience2589-00422025-07-0128711293110.1016/j.isci.2025.112931Deficiency of Rab26 causes behavioral defects in mice through impaired trafficking of serotonin (5-HT) transporterYandan Ren0Ziyan Wang1Ziheng Wei2Ruijuan Zhuang3Yongtao Zhang4Xiaoxi Liu5Cong Jiang6Xuan Liu7Ye Yun8Yanfang Li9Wanjin Hong10Tuanlao Wang11State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Fujian, ChinaState Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Fujian, ChinaState Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Fujian, ChinaState Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Fujian, ChinaState Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Fujian, ChinaState Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Fujian, ChinaState Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Fujian, ChinaState Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Fujian, ChinaState Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Fujian, ChinaInstitute of Neuroscience, School of Medicine, Xiamen University, Fujian, China; Corresponding authorState Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Fujian, China; Institute of Molecular and Cell Biology, A STAR (Agency of Science, Technology and Research), Singapore, Singapore; Corresponding authorState Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Fujian, China; Corresponding authorSummary: Rab proteins are key regulators of membrane trafficking. Dysregulated Rab proteins are associated with neurological diseases through the regulation of receptor endocytosis, recycling, and/or degradation. Rab26 is highly expressed in the brain, but its physiological function remains poorly elucidated. Here we demonstrate that Rab26 deficiency in mice causes depression and anxiety-like behaviors and cognitive impairment. The depletion of Rab26 results in the accumulation of synaptic vesicles in the presynaptic terminals and a decrease in the frequency of miniature excitatory postsynaptic currents (mEPSCs) and long-term potentiation (LTP). Mechanistically, Rab26 regulates the trafficking of serotonin (5-HT) transporter (SERT/Slc6a4). Rab26 interacts with SERT and promotes the autophagic degradation of SERT. Loss of Rab26 results in increased cell surface levels of SERT, suggesting that Rab26 plays a role in regulating the trafficking of SERT to maintain normal serotonin-mediated neurotransmission.http://www.sciencedirect.com/science/article/pii/S2589004225011927Natural sciencesBiological sciencesNeuroscienceBehavioral neuroscienceMolecular neuroscienceCellular neuroscience |
| spellingShingle | Yandan Ren Ziyan Wang Ziheng Wei Ruijuan Zhuang Yongtao Zhang Xiaoxi Liu Cong Jiang Xuan Liu Ye Yun Yanfang Li Wanjin Hong Tuanlao Wang Deficiency of Rab26 causes behavioral defects in mice through impaired trafficking of serotonin (5-HT) transporter iScience Natural sciences Biological sciences Neuroscience Behavioral neuroscience Molecular neuroscience Cellular neuroscience |
| title | Deficiency of Rab26 causes behavioral defects in mice through impaired trafficking of serotonin (5-HT) transporter |
| title_full | Deficiency of Rab26 causes behavioral defects in mice through impaired trafficking of serotonin (5-HT) transporter |
| title_fullStr | Deficiency of Rab26 causes behavioral defects in mice through impaired trafficking of serotonin (5-HT) transporter |
| title_full_unstemmed | Deficiency of Rab26 causes behavioral defects in mice through impaired trafficking of serotonin (5-HT) transporter |
| title_short | Deficiency of Rab26 causes behavioral defects in mice through impaired trafficking of serotonin (5-HT) transporter |
| title_sort | deficiency of rab26 causes behavioral defects in mice through impaired trafficking of serotonin 5 ht transporter |
| topic | Natural sciences Biological sciences Neuroscience Behavioral neuroscience Molecular neuroscience Cellular neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225011927 |
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