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Impairment of Release Site Clearance within the Active Zone by Reduced SCAMP5 Expression Causes Short-Term Depression of Synaptic Release

Research output: Contribution to journalArticle

  • Daehun Park
  • Unghwi Lee
  • Eunji Cho
  • Haiyan Zhao
  • Jung Ah Kim
  • Byoung Ju Lee
  • Philip Regan
  • Won Kyung Ho
  • Kwangwook Cho
  • Sunghoe Chang
Original languageEnglish
Pages (from-to)3339-3350
Number of pages12
JournalCell Reports
Volume22
Issue number12
Early online date20 Mar 2018
DOIs
DateAccepted/In press - 22 Feb 2018
DateE-pub ahead of print - 20 Mar 2018
DatePublished (current) - 20 Mar 2018

Abstract

Summary 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.

    Research areas

  • adaptor protein 2, autism spectrum disorder, endocytosis, presynaptic active zone, release site clearance, SCAMP5, secretory carrier membrane protein, short-term depression, super-resolution microscopy

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Elsevier at https://doi.org/10.1016/j.celrep.2018.02.088. Please refer to any applicable terms of use of the publisher.

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