![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
|
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
911kB | |
|
PDF (Supplemental Material)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
3MB |
| Item Type: | Article |
|---|---|
| Title: | The C-terminus of α-synuclein regulates its dynamic cellular internalization by neurexin 1β |
| Creators Name: | Birol, M. and Douzoglou Muñoz, I.I. and Rhoades, E. |
| Abstract: | The aggregation of the disordered neuronal protein, α-Synuclein (αS), is the primary pathological feature of Parkinson's disease. Current hypotheses favor cell-to-cell spread of αS species as underlying disease progression, driving interest in identifying the molecular species and cellular processes involved in cellular internalization of αS. Prior work from our lab identified the chemically specific interaction between αS and the pre-synaptic adhesion protein neurexin 1β (N1β) to be capable of driving cellular internalization of both monomer and aggregated forms of αS. Here we explore the physical basis of N1β-driven internalization of αS. Specifically, we show that spontaneous internalization of αS by SH-SY5Y and HEK293 cells expressing N1β requires essentially all of the membrane-binding domain of αS; αS constructs truncated beyond residue 90 bind to N1β in the plasma membrane of HEK cells, but are not internalized. Interestingly, prior to internalization, αS and N1β co-diffuse rapidly in the plasma membrane. αS constructs that are not internalized show very slow mobility themselves, as well as slow N1β diffusion. Finally, we find that truncated αS is capable of blocking internalization of full-length αS. Our results draw attention to the potential therapeutic value of blocking αS-N1β interactions. |
| Keywords: | alpha-Synuclein, alpha-Synuclein, HEK293 Cells, Neuroblastoma, Parkinson Disease |
| Source: | Molecular Biology of the Cell |
| ISSN: | 1059-1524 |
| Publisher: | American Society for Cell Biology |
| Volume: | 34 |
| Number: | 13 |
| Page Range: | br21 |
| Date: | 1 December 2023 |
| Official Publication: | https://doi.org/10.1091/mbc.E22-11-0496 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
Download Statistics
Download Statistics
