| First Author | Suzuki S | Year | 2011 |
| Journal | Biochem Biophys Res Commun | Volume | 408 |
| Issue | 4 | Pages | 582-8 |
| PubMed ID | 21531206 | Mgi Jnum | J:172403 |
| Mgi Id | MGI:5007601 | Doi | 10.1016/j.bbrc.2011.04.065 |
| Citation | Suzuki S, et al. (2011) AMSH is required to degrade ubiquitinated proteins in the central nervous system. Biochem Biophys Res Commun 408(4):582-8 |
| abstractText | 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. |
