AMSH is required to degrade ubiquitinated proteins in the central nervous system

Shunya Suzuki, Keiichi Tamai, Masahiko Watanabe, Masanao Kyuuma, Masao Ono, Kazuo Sugamura, Nobuyuki Tanaka

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Deubiquitination is a biochemical process that mediates the removal of ubiquitin moieties from ubiquitin-conjugated substrates. AMSH (associated molecule with the SH3 domain of STAM) is a deubiquitination enzyme that participates in the endosomal sorting of several cell-surface molecules. AMSH impairment results in missorted ubiquitinated cargoes in vitro and severe neurodegeneration in vivo, but it is not known how AMSH deficiency causes neuronal damage in the brain. Here, we demonstrate that AMSH-/- mice developed ubiquitinated protein accumulations as early as embryonic day 10 (E10), and that severe deposits were present in the brain at postnatal day 8 (P8) and P18. Interestingly, TDP-43 was found to accumulate and colocalize with glial marker-positive cells in the brain. Glutamate receptor and p62 accumulations were also found; these molecules colocalized with ubiquitinated aggregates in the brain. These data suggest that AMSH plays an important role in degrading ubiquitinated proteins and glutamate receptors in vivo. AMSH-/- mice provide an animal model for neurodegenerative diseases, which are commonly characterized by the generation of proteinaceous aggregates.

Original languageEnglish
Pages (from-to)582-588
Number of pages7
JournalBiochemical and biophysical research communications
Volume408
Issue number4
DOIs
Publication statusPublished - 2011 May 20
Externally publishedYes

Keywords

  • AMSH
  • Hippocampus
  • Neurodegeneration
  • Ubiquitin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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