Omics · study · 2026
Tubulin hyperglutamylation causes retinal degeneration by impairing the structural integrity of cilia and protein mistrafficking
Listed in NCBI GEO
Tubulins undergo various posttranslational modifications (PTMs) that confer diverse functions to microtubules.
Description
Tubulin polyglutamylation is dynamically regulated by glutamylation and deglutamylation. AGBL5 is a deglutamylase that specifically removes glutamate at the branching point.
Mutations in AGBL5 in humans are associated with retinitis pigmentosa, but the underlying mechanism remains undefined. Here, we generated an Aglb5 knockout mouse that showed tubulin hyperglutamylation in photoreceptors, resulting in progressive retinal degeneration. RNA-seq analysis revealed the altered ciliary function in the Agbl5 knockout.
Read the rest (2 more)
Transmission electron microscopy indicated an impaired inner scaffold in the connecting cilium (CC). Consequently, phototransduction proteins were mislocalized or downregulated in mutant rod and cone photoreceptors. Disk membranes in photoreceptor outer segments were disorganized.
Immunofluorescence revealed that the recruitment of IFT88, kinesin-II, and dynein-2 to the CC was affected, implicating defective intraflagellar transport (IFT). Collectively, these findings demonstrate that tubulin glutamylation homeostasis regulated by AGBL5 is critical for photoreceptor survival by maintaining the structural integrity of the CC and normal protein trafficking through IFT.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE305nnn/GSE305830 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305830 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1307978 ncbi.nlm.nih.gov/bioproject/PRJNA1307978 ↗
project · from NCBI GEO
- PubMed 42011761 pubmed.ncbi.nlm.nih.gov/42011761 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Microscopy 75% · RNA sequencing 65%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE305830 | 12 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[modality].local:modality:microscopy | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| 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 |