Differential recruitment of UBQLN2 to nuclear inclusions in the polyglutamine diseases HD and SCA3

Neurobiology of Disease

Henry L. Paulson¹  Eiko N. Minakawa²  Biswarathan Ramani³  Bo Wang³  Li Zeng³  Sean A. Merillat³  Maria do Carmo Costa³  Roger L. Albin³  Sara J. Tallaksen-Greene³  Matthew D. Perkins⁴ 

[1] Geriatrics Research Education and Clinical Center, VAAAHS, Ann Arbor, MI, USA;Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan;Department of Neurology, University of Michigan, Ann Arbor, MI, USA;Michigan Brain Bank, University of Michigan, Ann Arbor, MI, USA;

关键词: UBQLN2;    SCA3;    Huntington's disease;    Polyglutamine;    UBA;    UBL;   

DOI  :  

来源: DOAJ

【 摘 要 】

Accumulation of mutant polyglutamine proteins in intraneuronal inclusions is a hallmark of polyglutamine diseases. Impairment of protein clearance systems and sequestration of clearance-related proteins into inclusions occur in many protein folding diseases, including polyglutamine diseases. The ubiquitin-binding and proteasome adaptor protein UBQLN2 participates in protein homeostasis and localizes to inclusions in various neurodegenerative diseases. Employing mouse models and human brain tissue of Huntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3), we show that UBQLN2 is selectively recruited to inclusions in HD but not SCA3. Consistent with this result, in a cell-based system mutant HTT interacts with UBQLN2 through the UBA domain while the SCA3 disease protein ATXN3, a deubiquitinating enzyme, does not interact with UBQLN2. Differential recruitment of UBQLN2 to aggregates in HD and SCA3 underscores the heterogeneity of inclusions in polyglutamine diseases and suggests that components of neuronal protein quality control may be differentially perturbed in distinct polyQ diseases.

【 授权许可】

Unknown