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Series GSE145804 Query DataSets for GSE145804
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
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Submission date Feb 24, 2020
Last update date Feb 25, 2020
Contact name Lubov Nathanson
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)
GSM4333243 RA/noDox rep1
GSM4333244 RA/noDox rep2
GSM4333245 RA/noDox rep3
BioProject PRJNA608280
SRA SRP250480

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Supplementary file Size Download File type/resource
GSE145804_DESeq2_final.csv.gz 645.0 Kb (ftp)(http) CSV
GSE145804_DESeq2_final_norm.csv.gz 1.1 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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