Characterization of the zinc-induced Shank3 interactome of mouse synaptosome

Yeunkum Lee, Jae Ryun Ryu, Hyojin Kang, Yoonhee Kim, Shinhyun Kim, Yinhua Zhang, Chunmei Jin, Hyo Min Cho, Won Ki Kim, Woong Sun, Kihoon Han

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)581-586
Number of pages6
JournalBiochemical and biophysical research communications
Volume494
Issue number3-4
DOIs
Publication statusPublished - 2017 Dec 16

Bibliographical note

Funding Information:
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government Ministry of Science, ICT & Future Planning (MISP) [ NRF-2015R1C1A1A01052794 ], by the Brain Research Program through the NRF funded by the MISP [ NRF-2015M3C7A1028790 ], by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea [ HI16C0090 ], and by a Korea University grant.

Publisher Copyright:
© 2017 Elsevier Inc.

Keywords

  • Interactome
  • Mass spectrometry
  • Shank3
  • Synaptosome
  • Zinc

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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