Excel · study · 2026
Polycystin-2 functions as a calcium leak channel under endoplasmic reticulum stress to protect against myocardial ischemia
Listed in NCBI GEO
Unresolved endoplasmic reticulum (ER) stress is deleterious in cardiovascular diseases, including myocardial infarction (MI).
Description
Under adaptive ER stress, activation of the unfolded protein response (UPR) is accompanied by increased mitochondrial calcium at mitochondrial-endoplasmic reticulum contact sites (MERCs), which enhances metabolism and restores homeostasis. The identity of this calcium source and its interplay with the UPR is unclear.
We find that ER-localized polycystin 2 (PC2), a calcium channel, is upregulated in MI. PC2-knockout mice with MI exhibit worsened heart function and disrupted PERK, a key UPR marker. Under ER stress in both isolated cardiomyocytes and in vitro, PC2 facilitated an adaptive ER calcium leak.
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ER stress induced PC2 localization to MERCs, as assessed with the short ER- mitochondrial contact probe SPLICS. Pharmacological experiments demonstrated that PC2 requires activated PERK for mitochondrial calcium transfer. Pathological PC2 mutations impaired ER calcium leak, but full-length PC2 re-established PERK phosphorylation and ER calcium leak.
Thus, PC2 functions in a PERK-dependent manner under ER stress to provide mitochondrial calcium, and its upregulation is cardioprotective in MI.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE348nnn/GSE348330 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE348330 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1533467 ncbi.nlm.nih.gov/bioproject/PRJNA1533467 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Heart 75% · Myocardial infarction 75%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE348330 | 8 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[anatomy].local:anatomy:heart | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[disease].local:disease:myocardial-infarction | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |