气候变化领域集成服务门户(CCPortal): SCAMP5 plays a critical role in axonal trafficking and synaptic localization of NHE6 to adjust quantal size at glutamatergic synapses

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DOI	10.1073/pnas.2011371118
	SCAMP5 plays a critical role in axonal trafficking and synaptic localization of NHE6 to adjust quantal size at glutamatergic synapses
	Lee U.; Choi C.; Ryu S.H.; Park D.; Lee S.-E.; Kim K.; Kim Y.; Chang S.
发表日期	2021
ISSN	00278424
卷号	118 期号:2
英文摘要	Glutamate uptake into synaptic vesicles (SVs) depends on cation/H+ exchange activity, which converts the chemical gradient (ΔpH) into membrane potential (Δψ) across the SV membrane at the presynaptic terminals. Thus, the proper recruitment of cation/H+ exchanger to SVs is important in determining glutamate quantal size, yet little is known about its localization mechanism. Here, we found that secretory carrier membrane protein 5 (SCAMP5) interacted with the cation/H+ exchanger NHE6, and this interaction regulated NHE6 recruitment to glutamatergic presynaptic terminals. Protein-protein interaction analysis with truncated constructs revealed that the 2/3 loop domain of SCAMP5 is directly associated with the C-terminal region of NHE6. The use of optical imaging and electrophysiological recording showed that small hairpin RNA-mediated knockdown (KD) of SCAMP5 or perturbation of SCAMP5/NHE6 interaction markedly inhibited axonal trafficking and the presynaptic localization of NHE6, leading to hyperacidification of SVs and a reduction in the quantal size of glutamate release. Knockout of NHE6 occluded the effect of SCAMP5 KD without causing additional defects. Together, our results reveal that as a key regulator of axonal trafficking and synaptic localization of NHE6, SCAMP5 could adjust presynaptic strength by regulating quantal size at glutamatergic synapses. Since both proteins are autism candidate genes, the reduced quantal size by interrupting their interaction may underscore synaptic dysfunction observed in autism. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Autism; NHE6; Presynaptic terminal; Quantal size; SCAMP5
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181085
作者单位	Department of Physiology and Biomedical Sciences, Seoul National University, College of Medicine, Seoul, 03080, South Korea; Neuroscience Research Institute, Seoul National University, College of Medicine, Seoul, 03080, South Korea
推荐引用方式 GB/T 7714	Lee U.,Choi C.,Ryu S.H.,et al. SCAMP5 plays a critical role in axonal trafficking and synaptic localization of NHE6 to adjust quantal size at glutamatergic synapses[J],2021,118(2).
APA	Lee U..,Choi C..,Ryu S.H..,Park D..,Lee S.-E..,...&Chang S..(2021).SCAMP5 plays a critical role in axonal trafficking and synaptic localization of NHE6 to adjust quantal size at glutamatergic synapses.Proceedings of the National Academy of Sciences of the United States of America,118(2).
MLA	Lee U.,et al."SCAMP5 plays a critical role in axonal trafficking and synaptic localization of NHE6 to adjust quantal size at glutamatergic synapses".Proceedings of the National Academy of Sciences of the United States of America 118.2(2021).