Dhungel et al. 2014 (PRJNA270712)

General Details

Title Parkinson's disease genes VPS35 and EIF4G1 interact genetically and converge on alpha-synuclein
Organism
Number of Samples 4
Release Date 2014/12/18 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP051314
ENA SRP051314
GEO
BioProject PRJNA270712

Publication

Title
Authors Dhungel N,Eleuteri S,Li LB,Kramer NJ,Chartron JW,Spencer B,Kosberg K,Fields JA,Stafa K,Adame A,Lashuel H,Frydman J,Shen K,Masliah E,Gitler AD
Journal Neuron
Publication Date 2015 Jan 7
Abstract Parkinson's disease (PD) is a common neurodegenerative disorder. Functional interactions between some PD genes, like PINK1 and parkin, have been identified, but whether other ones interact remains elusive. Here we report an unexpected genetic interaction between two PD genes, VPS35 and EIF4G1. We provide evidence that EIF4G1 upregulation causes defects associated with protein misfolding. Expression of a sortilin protein rescues these defects, downstream of VPS35, suggesting a potential role for sortilins in PD. We also show interactions between VPS35, EIF4G1, and α-synuclein, a protein with a key role in PD. We extend our findings from yeast to an animal model and show that these interactions are conserved in neurons and in transgenic mice. Our studies reveal unexpected genetic and functional interactions between two seemingly unrelated PD genes and functionally connect them to α-synuclein pathobiology in yeast, worms, and mouse. Finally, we provide a resource of candidate PD genes for future interrogation. Copyright © 2015 Elsevier Inc. All rights reserved.
PMC PMC4289081
PMID 25533483
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR1722638 PRJNA270712 Saccharomyces cerevisiae Ribo-Seq Cycloheximide
SRR1722639 PRJNA270712 Saccharomyces cerevisiae Ribo-Seq Cycloheximide
SRR1722640 PRJNA270712 Saccharomyces cerevisiae Ribo-Seq Cycloheximide
SRR1722641 PRJNA270712 Saccharomyces cerevisiae Ribo-Seq Cycloheximide
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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