SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function
Publication in refereed journal

香港中文大學研究人員
替代計量分析
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其它資訊
摘要Glycine transporters (GlyT1 and GlyT2) that regulate levels of brain glycine, an inhibitory neurotransmitter with co-agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizophrenia. However, it remains unclear whether other amino acid transporters expressed in the brain can also regulate brain glycine levels and NMDAR function. Here, we report that SLC6A20A, an amino acid transporter known to transport proline based on in vitro data but is understudied in the brain, regulates proline and glycine levels and NMDAR function in the mouse brain. SLC6A20A transcript and protein levels were abnormally increased in mice carrying a mutant PTEN protein lacking the C terminus through enhanced β-catenin binding to the Slc6a20a gene. These mice displayed reduced extracellular levels of brain proline and glycine and decreased NMDAR currents. Elevating glycine levels back to normal ranges by antisense oligonucleotide-induced SLC6A20 knockdown, or the competitive GlyT1 antagonist sarcosine, normalized NMDAR currents and repetitive climbing behavior observed in these mice. Conversely, mice lacking SLC6A20A displayed increased extracellular glycine levels and NMDAR currents. Lastly, both mouse and human SLC6A20 proteins mediated proline and glycine transports, and SLC6A20 proteins could be detected in human neurons. These results suggest that SLC6A20 regulates proline and glycine homeostasis in the brain and that SLC6A20 inhibition has therapeutic potential for brain disorders involving NMDAR hypofunction.
著者Bae M, Roh JD, Kim Y, Kim SS, Han HM, Yang E, Kang H, Lee S, Kim JY, Kang R, Jung H, Yoo T, Kim H, Kim D, Oh H, Han S, Kim D, Han J, Bae YC, Kim H, Ahn S, Chan AM, Lee D, Kim JW, Kim E
期刊名稱EMBO Molecular Medicine
出版年份2021
月份2
卷號13
期次2
出版社Wiley
文章號碼e12632
國際標準期刊號1757-4676
語言英式英語
關鍵詞NMDA receptor, PTEN, Slc6a20, glycine transporter, neuropsychiatric disorders

上次更新時間 2021-20-06 於 23:57