Kavli Affiliate: V. S. Ramachandran
| Authors: Victoria Paradise, Malavika Sabu, Joanna Bafia, Nyle A Sharif, Chi Nguyen, Rijuta Dhanraj Mukim, Kalin D Konrad-Vicario, Xiao Wang, Bianca T Corjuc, Jack Fu, Gabriella Maldonado, Jeffrey Ndubisi, Michael Strickland, Helen Figueroa, Douglas L Almeida, Bradley T Hyman, David M Holtzman, Tal Nuriel and Kapil V Ramachandran
| Summary:
Neuroproteasomes are a subset of 20S proteasomes that are localized to the neuronal plasma membrane and degrade newly synthesized proteins. To date, the molecular composition of neuroproteasomes is undefined, and moreover, whether neuroproteasomes can influence protein aggregation with relevance to neurodegenerative disorders remains unexplored. Using a Cre-dependent conditional knock-in mouse line to endogenously tag the proteasome, we find that neuroproteasomes co-purify with ApoE, the most significant risk factor for late-onset Alzheimer’s Disease (AD). We discover that neuroproteasome membrane localization is differentially modulated by ApoE isoforms (E4