| Title: |
Mutations in Tau’s Proline Rich Domain Affect its Protein Interactions |
| Authors: |
Koutures, Anne; Katz, Brittany; Hwang, Kaylin; Cohn, Whitaker; Addo‐Osafo, Kwaku; Vossel, Keith |
| Source: |
Alzheimer's & Dementia ; volume 20, issue S1 ; ISSN 1552-5260 1552-5279 |
| Publisher Information: |
Wiley |
| Publication Year: |
2024 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Background Epileptic activity is increasingly recognized as a contributor to Alzheimer’s Disease (AD) pathology. In AD models, endogenous tau contributes to epileptic activity and associated cognitive deficits through mechanisms that are not fully understood. Increased attention is being directed towards tau’s interactions with proteins that regulate neuronal activity, particularly tau’s proline rich domain and its binding to SH3‐containing proteins. However, the impact of mutations in tau’s proline‐rich region on other protein interactions remains unclear. Method We assessed mutations in tau’s proline rich domain in two mouse lines: AxxA6 (P‐to‐A substitutions in 6th PxxP motif in tau) and R221A (R‐to‐A substitution at amino acid corresponding to 221 in human 2N4R tau). These mutations block tau’s interactions with SH3‐containing proteins, including PLCγ1 and p85α/PI3K. Co‐immunoprecipitation (Co‐IP) of tau from cortical brain tissue was confirmed and analyzed by mass spectrometry. We compared protein abundance ratios to wild type tau mice within each mouse line. Significant (p |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1002/alz.089653 |
| Availability: |
https://doi.org/10.1002/alz.089653 |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.4CDC74AB |
| Database: |
BASE |