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 language | English |
|---|---|
| Pages (from-to) | 581-586 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 494 |
| Issue number | 3-4 |
| DOIs | |
| Publication status | Published - 2017 Dec 16 |
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Keywords
- Interactome
- Mass spectrometry
- Shank3
- Synaptosome
- Zinc
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Characterization of the zinc-induced Shank3 interactome of mouse synaptosome. / Lee, Yeunkum; Ryu, Jae Ryun; Kang, Hyojin; Kim, Yoonhee; Kim, Shinhyun; Zhang, Yinhua; Jin, Chunmei; Cho, Hyo Min; Kim, Won-Ki; Sun, Woong; Han, Kihoon.
In: Biochemical and Biophysical Research Communications, Vol. 494, No. 3-4, 16.12.2017, p. 581-586.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Characterization of the zinc-induced Shank3 interactome of mouse synaptosome
AU - Lee, Yeunkum
AU - Ryu, Jae Ryun
AU - Kang, Hyojin
AU - Kim, Yoonhee
AU - Kim, Shinhyun
AU - Zhang, Yinhua
AU - Jin, Chunmei
AU - Cho, Hyo Min
AU - Kim, Won-Ki
AU - Sun, Woong
AU - Han, Kihoon
PY - 2017/12/16
Y1 - 2017/12/16
N2 - 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.
AB - 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.
KW - Interactome
KW - Mass spectrometry
KW - Shank3
KW - Synaptosome
KW - Zinc
UR - http://www.scopus.com/inward/record.url?scp=85032333964&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032333964&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2017.10.143
DO - 10.1016/j.bbrc.2017.10.143
M3 - Article
C2 - 29111324
AN - SCOPUS:85032333964
VL - 494
SP - 581
EP - 586
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3-4
ER -