|
| Status |
Public on Feb 24, 2020 |
| Title |
α-Synuclein Translocates To The Nucleus To Activate Retinoic Acid- Dependent Gene Transcription |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
α-Synuclein (α-Syn) is a protein implicated in the pathogenesis of Parkinson’s disease (PD). It is primarily cytosolic and reversibly interacts with cell membranes. α-Syn also occurs in the nucleus, however, the mechanisms involved in its nuclear localization are poorly understood. We analyzed alterations in gene expression following induced α-Syn expression in SH-SY5Y cells. Analysis for upstream regulators pointed at alterations in transcription activity of retinoic acid receptors (RAR)s and additional nuclear receptors. We show that α-Syn binds RA and translocates to the nucleus to selectively enhance gene transcription. Nuclear translocation of α-Syn is regulated by calreticulin, in a leptomycin-B independent mechanism. Importantly, nuclear translocation of α-Syn following RA treatment enhances its toxicity in cultured neurons and the expression levels of PD-associated genes, among which are two familial PDassociated genes, ATPase cation transporting 13A2 (ATP13A2) and PTEN-induced kinase 1 (PINK1). The results link a physiological role for α-Syn in the regulation of RAmediated gene transcription and its toxicity in the synucleinopathies.
|
| |
|
| Overall design |
SH-SY5Y cells induced to express α-Syn (with 1 μg/ml doxycycline) and treated for 16 hours in DMEM supplemented with 0.1% serum and RA (5 μM). Cells were collected and analyzed following 72 hours from induction of α-Syn expression. Control samples included an identical set up but without induced α-Syn expression.
|
| |
|
| Contributor(s) |
Davidi D, Schechter M, Abd ElHadi S, Matatov A, Nathanson L, Sharon R |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Feb 24, 2020 |
| Last update date |
Feb 25, 2020 |
| Contact name |
Lubov Nathanson |
| E-mail(s) |
lnathanson@nova.edu
|
| Organization name |
Nova Southeastern University
|
| Department |
INIM
|
| Street address |
3321 College Ave.
|
| City |
Fort Lauderdale |
| State/province |
Florida |
| ZIP/Postal code |
33314 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
|
| Samples (12)
|
|
| Relations |
| BioProject |
PRJNA608280 |
| SRA |
SRP250480 |
Less...
More...