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
N1 - Funding Information:
Acknowledgements This work was supported by National Research Foundation of Korea (NRF) Grants funded by the Korea Government Ministry of Science and ICT (NRF-2018R1C1B6001235, NRF-2018M3C7A1024603, NRF-2018R1A6A3A11040508).
Publisher Copyright:
© 2018, The Pharmaceutical Society of Korea.
PY - 2019/4/1
Y1 - 2019/4/1
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 - PSD-95
KW - Postsynaptic density
UR - http://www.scopus.com/inward/record.url?scp=85053879766&partnerID=8YFLogxK
U2 - 10.1007/s12272-018-1081-8
DO - 10.1007/s12272-018-1081-8
M3 - Review article
C2 - 30259348
AN - SCOPUS:85053879766
SN - 0253-6269
VL - 42
SP - 285
EP - 292
JO - Archives of Pharmacal Research
JF - Archives of Pharmacal Research
IS - 4
ER -