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DOI10.1073/PNAS.2011870117
Hidden proteome of synaptic vesicles in the mammalian brain
Taoufiq Z.; Ninov M.; Villar-Briones A.; Wang H.-Y.; Sasaki T.; Roy M.C.; Beauchain F.; Mori Y.; Yoshida T.; Takamori S.; Jahn R.; Takahashi T.
发表日期2021
ISSN00278424
起始页码33586
结束页码33596
卷号117期号:52
英文摘要Current proteomic studies clarified canonical synaptic proteins that are common to many types of synapses. However, proteins of diversified functions in a subset of synapses are largely hidden because of their low abundance or structural similarities to abundant proteins. To overcome this limitation, we have developed an “ultra-definition” (UD) subcellular proteomic workflow. Using purified synaptic vesicle (SV) fraction from rat brain, we identified 1,466 proteins, three times more than reported previously. This refined proteome includes all canonical SV proteins, as well as numerous proteins of low abundance, many of which were hitherto undetected. Comparison of UD quantifications between SV and synaptosomal fractions has enabled us to distinguish SV-resident proteins from potential SV-visitor proteins. We found 134 SV residents, of which 86 are present in an average copy number per SV of less than one, including vesicular transporters of nonubiquitous neurotransmitters in the brain. We provide a fully annotated resource of all categorized SV-resident and potential SV-visitor proteins, which can be utilized to drive novel functional studies, as we characterized here Aak1 as a regulator of synaptic transmission. Moreover, proteins in the SV fraction are associated with more than 200 distinct brain diseases. Remarkably, a majority of these proteins was found in the low-abundance proteome range, highlighting its pathological significance. Our deep SV proteome will provide a fundamental resource for a variety of future investigations on the function of synapses in health and disease. © 2020 National Academy of Sciences. All rights reserved.
英文关键词Brain disorders; Deep proteomics; Neurotransmission; Synapse; Synaptic vesicles
语种英语
scopus关键词neurotransmitter; proteome; nerve protein; peptide; proteome; animal experiment; Article; brain disease; controlled study; gene dosage; neurotransmission; nonhuman; pathology; priority journal; protein analysis; proteomics; rat; synapse vesicle; synaptic transmission; workflow; amino acid sequence; animal; brain; chemistry; mammal; metabolism; Sprague Dawley rat; synapse vesicle; synaptosome; ultrastructure; Amino Acid Sequence; Animals; Brain; Mammals; Nerve Tissue Proteins; Peptides; Proteome; Proteomics; Rats, Sprague-Dawley; Synaptic Transmission; Synaptic Vesicles; Synaptosomes
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/179683
作者单位Cellular and Molecular Synaptic Function Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, 904-0495, Japan; Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, D-37077, Germany; Instrumental Analysis Section, Okinawa Institute of Science and Technology, Graduate University, Okinawa, 904-0495, Japan; Imaging Section, Okinawa Institute of Science and Technology, Graduate University, Okinawa, 904-0495, Japan; Laboratory of Neural Membrane Biology, Graduate School of Brain Science, Doshisha University, Kyoto, 610-0394, Japan
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GB/T 7714
Taoufiq Z.,Ninov M.,Villar-Briones A.,et al. Hidden proteome of synaptic vesicles in the mammalian brain[J],2021,117(52).
APA Taoufiq Z..,Ninov M..,Villar-Briones A..,Wang H.-Y..,Sasaki T..,...&Takahashi T..(2021).Hidden proteome of synaptic vesicles in the mammalian brain.Proceedings of the National Academy of Sciences of the United States of America,117(52).
MLA Taoufiq Z.,et al."Hidden proteome of synaptic vesicles in the mammalian brain".Proceedings of the National Academy of Sciences of the United States of America 117.52(2021).
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