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Cell Reports, Volume 22, Issue 12, 20 March 2018, Pages 3339-3350, DOI: https://doi.org/10.1016/j.celrep.2018.02.088 Impairment of Release Site Clearance within the Active Zone by Reduced SCAMP5 Expression Causes Short-Term Depression of Synaptic Release

Daehun Park,¹ Unghwi Lee,¹ Eunji Cho,¹ Haiyan Zhao,² Jung Ah Kim,^1,3 Byoung Ju Lee,¹ Philip Regan,⁴ Won-Kyung Ho,^1,5 Kwangwook Cho,^4,6 and Sunghoe Chang^1,3,5,7,*¹Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea

²Physical Examination Center, Department of Internal Medicine, Yanbian University Hospital, Yanji, Jilin Province, China

³Neuroscience Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea

⁴Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, UK

⁵Biomembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul, South Korea

⁶Present address: Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

⁷Lead Contact

^*Correspondence : Sunghoe Chang

Abstract

Despite being a highly enriched synaptic vesicle (SV) protein and a candidate gene for autism, the physiological function of SCAMP5 remains mostly enigmatic. Here, using optical imaging and electrophysiological experiments, we demonstrate that SCAMP5 plays a critical role in release site clearance at the active zone. Truncation analysis revealed that the 2/3 loop domain of SCAMP5 directly interacts with adaptor protein 2, and this interaction is critical for its role in release site clearance. Knockdown (KD) of SCAMP5 exhibited pronounced synaptic depression accompanied by a slower recovery of the SV pool. Moreover, it induced a strong frequency-dependent short-term depression of synaptic release, even under the condition of sufficient release-ready SVs. Super-resolution microscopy further proved the defects in SV protein clearance induced by KD. Thus, reduced expression of SCAMP5 may impair the efficiency of SV clearance at the active zone, and this might relate to the synaptic dysfunction observed in autism.

논문정보

형식Research article
게재일2018년 03월 (BRIC 등록일 2018-04-17)
연구진국내(교신)+국외 연구진
분야 의약학 > 신경의학
구분구・추천논문

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