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Plekhg5 regulates the unconventional secretion of Sod1 by presynaptic secretory autophagy

GSE269588 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2024/08/28 Platform GPL19057
At a glance

RNA-seq (gene expression) · mouse · 12 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
12 samples: 3 × Plekhg5+/+ # vs 3 × Plekhg5-/- # vs 3 × Plekhg5+/+ SOD1-G93A # vs 3 × Plekhg5-/- SOD1-G93A #Groups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagyNature communications · 2024
Summary (written by the submitters)
Increasing evidence suggests an essential function for autophagy in unconventional protein secretion (UPS). However, despite its relevance for the secretion of aggregate-prone proteins, the mechanisms of secretory autophagy in neurons have remained elusive. Here we show that the lower motoneuron disease-associated protein Plekhg5 drives the UPS of Sod1.
Read the full summary ↓
Mechanistically, Sod1 is sequestered into the intermembrane space of autophagosomes which fuse with secretory lysosomal-related organelles (LROs). Deletion of Plekhg5 in mice disrupts the secretion of these LROs causing Sod1 accumulation at swollen presynaptic sites. A reduced secretion of toxic ALS-linked SOD1G93A following deletion of Plekhg5 in SOD1G93A mice accelerated disease onset while prolonging survival due to an attenuated microglia activation. Using human isogenic iPSC-derived motoneurons we show an impaired secretion of ALS-linked SOD1D90A, which coincided with a reduced PLEKHG5 expression. Our findings highlight an unexpected pathophysiological mechanism that converges two motoneuron disease-associated proteins into a common pathway.
Published in
Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagy
Hutchings AJ, Hambrecht B, Veh A et al. · Nature communications 2024 · PMID 39366938 · doi:10.1038/s41467-024-52875-5
This dataset
Open GSE269588 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE269588_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1122581 and SRA study SRP513232. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39366938) ↗
Study design
3 × Plekhg5+/+ # vs 3 × Plekhg5-/- # vs 3 × Plekhg5+/+ SOD1-G93A # vs 3 × Plekhg5-/- SOD1-G93A #

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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