Abstract
In the mammalian brain, neuronal excitatory synaptic development, function, and plasticity largely rely on dynamic, activity-dependent changes in the macromolecular protein complex called the postsynaptic density (PSD). Activity-dependent Lys48-linked polyubiquitination and subsequent proteasomal degradation of key proteins in the PSD have been reported. However, investigations into the functions and regulatory mechanisms of Lys63-linked polyubiquitination, the second most abundant polyubiquitin form in synapses, have recently begun. Recent studies showed that a Lys63 linkage-specific deubiquitinase (DUB), cylindromatosis-associated DUB (CYLD) localizes to the PSD where its DUB activity is regulated by different kinases. In addition, Lys63-linked polyubiquitination of postsynaptic density 95 (PSD-95), a core scaffolding protein of the PSD, was identified and its functional significance in synaptic plasticity was characterized. In this review, we summarize these recent findings on Lys63-linked polyubiquitination in excitatory postsynapses, and also propose key questions and prospects about this emerging type of posttranslational modification of the PSD proteome.
| Original language | English |
|---|---|
| Journal | Archives of Pharmacal Research |
| DOIs | |
| Publication status | Accepted/In press - 2018 Jan 1 |
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Keywords
- CYLD
- Excitatory postsynapse
- Lys63-linked polyubiquitination
- Postsynaptic density
- PSD-95
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
- Organic Chemistry
Cite this
Emerging roles of Lys63-linked polyubiquitination in neuronal excitatory postsynapses. / Kim, Shinhyun; Zhang, Yinhua; Jin, Chunmei; Lee, Yeunkum; Kim, Yoonhee; Han, Kihoon.
In: Archives of Pharmacal Research, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Emerging roles of Lys63-linked polyubiquitination in neuronal excitatory postsynapses
AU - Kim, Shinhyun
AU - Zhang, Yinhua
AU - Jin, Chunmei
AU - Lee, Yeunkum
AU - Kim, Yoonhee
AU - Han, Kihoon
PY - 2018/1/1
Y1 - 2018/1/1
N2 - In the mammalian brain, neuronal excitatory synaptic development, function, and plasticity largely rely on dynamic, activity-dependent changes in the macromolecular protein complex called the postsynaptic density (PSD). Activity-dependent Lys48-linked polyubiquitination and subsequent proteasomal degradation of key proteins in the PSD have been reported. However, investigations into the functions and regulatory mechanisms of Lys63-linked polyubiquitination, the second most abundant polyubiquitin form in synapses, have recently begun. Recent studies showed that a Lys63 linkage-specific deubiquitinase (DUB), cylindromatosis-associated DUB (CYLD) localizes to the PSD where its DUB activity is regulated by different kinases. In addition, Lys63-linked polyubiquitination of postsynaptic density 95 (PSD-95), a core scaffolding protein of the PSD, was identified and its functional significance in synaptic plasticity was characterized. In this review, we summarize these recent findings on Lys63-linked polyubiquitination in excitatory postsynapses, and also propose key questions and prospects about this emerging type of posttranslational modification of the PSD proteome.
AB - In the mammalian brain, neuronal excitatory synaptic development, function, and plasticity largely rely on dynamic, activity-dependent changes in the macromolecular protein complex called the postsynaptic density (PSD). Activity-dependent Lys48-linked polyubiquitination and subsequent proteasomal degradation of key proteins in the PSD have been reported. However, investigations into the functions and regulatory mechanisms of Lys63-linked polyubiquitination, the second most abundant polyubiquitin form in synapses, have recently begun. Recent studies showed that a Lys63 linkage-specific deubiquitinase (DUB), cylindromatosis-associated DUB (CYLD) localizes to the PSD where its DUB activity is regulated by different kinases. In addition, Lys63-linked polyubiquitination of postsynaptic density 95 (PSD-95), a core scaffolding protein of the PSD, was identified and its functional significance in synaptic plasticity was characterized. In this review, we summarize these recent findings on Lys63-linked polyubiquitination in excitatory postsynapses, and also propose key questions and prospects about this emerging type of posttranslational modification of the PSD proteome.
KW - CYLD
KW - Excitatory postsynapse
KW - Lys63-linked polyubiquitination
KW - Postsynaptic density
KW - PSD-95
UR - http://www.scopus.com/inward/record.url?scp=85053879766&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053879766&partnerID=8YFLogxK
U2 - 10.1007/s12272-018-1081-8
DO - 10.1007/s12272-018-1081-8
M3 - Article
C2 - 30259348
AN - SCOPUS:85053879766
JO - Archives of Pharmacal Research
JF - Archives of Pharmacal Research
SN - 0253-6269
ER -