Next Article in Journal
A Highlight on the Inhibition of Fungal Carbonic Anhydrases as Drug Targets for the Antifungal Armamentarium
Previous Article in Journal
Analysis of Astroglial Secretomic Profile in the Mecp2-Deficient Male Mouse Model of Rett Syndrome
Article

Impaired 26S Proteasome Assembly Precedes Neuronal Loss in Mutant UBQLN2 Rats

Department of Pathology, Anatomy & Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Fabrizio Michetti
Int. J. Mol. Sci. 2021, 22(9), 4319; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094319
Received: 31 March 2021 / Revised: 15 April 2021 / Accepted: 19 April 2021 / Published: 21 April 2021
(This article belongs to the Section Molecular Neurobiology)
Proteasomal dysfunction is known to be associated with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS/FTD). Our previous reports have shown that a mutant form of ubiquilin-2 (UBQLN2) linked to ALS/FTD leads to neurodegeneration accompanied by accumulations of the proteasome subunit Rpt1 in transgenic rats, but the precise pathogenic mechanisms of how this mutation impairs the proteasome remains to be elucidated. Here, we reveal that this UBQLN2 mutation in rats disrupted the proteasome integrity prior to neurodegeneration, that it dissociated the 26S proteasome in vitro, and that its depletion did not affect 26S proteasome assembly. During both disease progression and in an age-dependent manner, we found that proteasome subunits were translocated to the nucleus, including both of the 20S core particles (PSMA1 and PSMB7) and the 19S regulatory particles (Rpt1 and Rpn1), suggesting that defective proteasome function may result from the proteasome-subunit mislocalization. Taken together, the present data demonstrate that impaired proteasome assembly is an early event in the pathogenesis of UBQLN2-associated neurodegeneration in mutant UBQLN2 rats. View Full-Text
Keywords: ALS; FTD; UBQLN2; proteasome; protein aggregation; rat ALS; FTD; UBQLN2; proteasome; protein aggregation; rat
Show Figures

Figure 1

MDPI and ACS Style

Zhang, W.; Huang, B.; Gao, L.; Huang, C. Impaired 26S Proteasome Assembly Precedes Neuronal Loss in Mutant UBQLN2 Rats. Int. J. Mol. Sci. 2021, 22, 4319. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094319

AMA Style

Zhang W, Huang B, Gao L, Huang C. Impaired 26S Proteasome Assembly Precedes Neuronal Loss in Mutant UBQLN2 Rats. International Journal of Molecular Sciences. 2021; 22(9):4319. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094319

Chicago/Turabian Style

Zhang, Wenjuan, Bo Huang, Limo Gao, and Cao Huang. 2021. "Impaired 26S Proteasome Assembly Precedes Neuronal Loss in Mutant UBQLN2 Rats" International Journal of Molecular Sciences 22, no. 9: 4319. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094319

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop