Characterization of the zinc-induced Shank3 interactome of mouse synaptosome
Autor: | Yoonhee Kim, Woong Sun, Hyojin Kang, Chunmei Jin, Hyo Min Cho, Yinhua Zhang, Jae Ryun Ryu, Won Ki Kim, Yeunkum Lee, Kihoon Han, Shinhyun Kim |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Scaffold protein Mitochondrial Diseases Proteome Biophysics chemistry.chemical_element Mice Transgenic Nerve Tissue Proteins Zinc Mitochondrion Biology Biochemistry Interactome Protein–protein interaction Mice 03 medical and health sciences Chlorides Protein Interaction Mapping Animals Humans Protein Interaction Maps Molecular Biology Synaptosome Brain Diseases Dose-Response Relationship Drug Microfilament Proteins Cell Biology 030104 developmental biology chemistry Zinc Compounds Metabolome Excitatory postsynaptic potential Postsynaptic density Synaptosomes |
Zdroj: | Biochemical and Biophysical Research Communications. 494:581-586 |
ISSN: | 0006-291X |
Popis: | Variants of the SHANK3 gene, which encodes a core scaffold protein of the postsynaptic density of excitatory synapses, have been causally associated with numerous brain disorders. Shank3 proteins directly bind zinc ions through their C-terminal sterile α motif domain, which enhances the multimerization and synaptic localization of Shank3, to regulate excitatory synaptic strength. However, no studies have explored whether zinc affects the protein interactions of Shank3, which might contribute to the synaptic changes observed after zinc application. To examine this, we first purified Shank3 protein complexes from mouse brain synaptosomal lysates that were incubated with different concentrations of ZnCl2, and analyzed them with mass spectrometry. We used strict criteria to identify 71 proteins that specifically interacted with Shank3 when extra ZnCl2 was added to the lysate. To characterize the zinc-induced Shank3 interactome, we performed various bioinformatic analyses that revealed significant associations of the interactome with subcellular compartments, including mitochondria, and brain disorders, such as bipolar disorder and schizophrenia. Together, our results showing that zinc affected the Shank3 protein interactions of in vitro mouse synaptosomes provided an additional link between zinc and core synaptic proteins that have been implicated in multiple brain disorders. |
Databáze: | OpenAIRE |
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