Emerging roles of Lys63-linked polyubiquitination in neuronal excitatory postsynapses

Shinhyun Kim, Yinhua Zhang, Chunmei Jin, Yeunkum Lee, Yoonhee Kim, Kihoon Han

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish
JournalArchives of Pharmacal Research
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Fingerprint

Post-Synaptic Density
Plasticity
Polyubiquitin
Multiprotein Complexes
Proteome
Brain
Phosphotransferases
Degradation
Neuronal Plasticity
Post Translational Protein Processing
Synapses
Proteins
Deubiquitinating Enzymes
postsynaptic density proteins

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 journalArticle

Kim, Shinhyun ; Zhang, Yinhua ; Jin, Chunmei ; Lee, Yeunkum ; Kim, Yoonhee ; Han, Kihoon. / Emerging roles of Lys63-linked polyubiquitination in neuronal excitatory postsynapses. In: Archives of Pharmacal Research. 2018.
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