Omics · study · 2026
GABARAPs proteins modulate FVIII secretion in molecule-specific manner via energy related pathways
Listed in NCBI GEO
Little is known about the biogenesis of Factor VIII (FVIII), its control of expression, intracellular trafficking, secretion, and associated cellular energy requirements.
Description
In this project, we employed a Y2H approach in to identify new interacting proteins that may play a role in the above mentioned processes. As a result, we successfully isolated GABARAP, an ATG8 protein, as a potential interactor with the FVIII-B domain.
While GABARAP did not co-immunoprecipitate with FVIII, we observed a weak interaction with full-length FVIII (FL-FVIII) but not with the B-domain-deleted FVIII (BDD-FVIII) using the BLITZ system. Additionally, there was a significant increase in the co-localization of GABARAP with FL-FVIII compared to BDD-FVIII. Furthermore, both transient knockdown of GABARAP through siRNA and stable knockout using CRISPR resulted in a decrease in FVIII secretion.
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Similar effects on FVIII secretion were observed for knockouts of MCFD2, LMAN1, and Calreticulin, while a contrasting effect, increasing secretion, was seen for knockouts of Calnexin, GABARAPL1, GABARAPL2, and ATG7. To explain the differential effects on FVIII secretion, we examined the expression profiles of the knockouts and the wild-type clones, revealing differences in several pathways, notably energy related oxidative phosphorylation and mitochondrial function.
The residual cellular ATP content and cellular mitochondrial function showed a strong correlation with FVIII secretion levels. These findings establish a link between GABARAP proteins, the cellular energy status, and FVIII secretion.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE269nnn/GSE269206 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE269206 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1120569 ncbi.nlm.nih.gov/bioproject/PRJNA1120569 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE269206 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| 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:9606 | 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 |