Characterization of the zinc-induced Shank3 interactome of mouse synaptosome

Biochem Biophys Res Commun. 2017 Dec 16;494(3-4):581-586. doi: 10.1016/j.bbrc.2017.10.143. Epub 2017 Oct 28.


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.

Keywords: Interactome; Mass spectrometry; Shank3; Synaptosome; Zinc.

MeSH terms

  • Animals
  • Brain Diseases / metabolism*
  • Chlorides / administration & dosage*
  • Dose-Response Relationship, Drug
  • Humans
  • Metabolome / drug effects
  • Metabolome / physiology
  • Mice
  • Mice, Transgenic
  • Microfilament Proteins
  • Mitochondrial Diseases / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Interaction Mapping / methods
  • Protein Interaction Maps / drug effects
  • Protein Interaction Maps / physiology*
  • Proteome / drug effects
  • Proteome / metabolism*
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism*
  • Zinc Compounds / administration & dosage*


  • Chlorides
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Proteome
  • Shank3 protein, mouse
  • Zinc Compounds
  • zinc chloride