ArticleThe Journal of biological chemistry2022
A highly conserved zebrafish IMPDH retinal isoform produces the majority of guanine and forms dynamic protein filaments in photoreceptor cells.
Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Disease progression in IMPDH1 gene-associated rod-cone dystrophy caused by a rare p.Thr244Pro heterozygous variant.Documenta ophthalmologica. Advances in ophthalmology · 2026Article
- Conserved and lineage-specific mechanisms drive chromatophore differentiation in reptiles.Nature communications · 2026Article
- IMPDH and GTP Metabolism in Cancer: Mechanisms, Regulation, and Translational Scope.Cancer science · 2025Review
- Retinopathy-associated inosine monophosphate dehydrogenase 1 mutations cause metabolic and filament defects in cones.Disease models & mechanisms · 2025Article
- Appendage regeneration requires IMPDH2 and creates a sensitized environment for enzyme filament formation.bioRxiv : the preprint server for biology · 2024Article
- What Makes a Mimic? Orange, Red, and Black Color Production in the Mimic Poison Frog (Ranitomeya imitator).Genome biology and evolution · 2024Article
- Light-sensitive phosphorylation regulates retinal IMPDH1 activity and filament assembly.The Journal of cell biology · 2024Article
- Greater than the sum of parts: Mechanisms of metabolic regulation by enzyme filaments.Current opinion in structural biology · 2023Review
- Effect on cell survival and cytoophidium assembly of the adRP-10-related IMPDH1 missense mutation Asp226Asn.Frontiers in cell and developmental biology · 2023Article
- Metabolism Dysregulation in Retinal Diseases and Related Therapies.Antioxidants (Basel, Switzerland) · 2022Review
- IMPDH dysregulation in disease: a mini review.Biochemical Society transactions · 2022Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Inosine monophosphate dehydrogenase (IMPDH) is a key regulatory enzyme in the de novo synthesis of the purine base guanine. Dominant mutations in human IMPDH1 cause photoreceptor degeneration for reasons that are unknown. Here, we sought to provide some foundational information on Impdh1a in the zebrafish retina. We found that in zebrafish, gene subfunctionalization due to ancestral duplication resulted in a predominant retinal variant expressed exclusively in rod and cone photoreceptors. This variant is structurally and functionally similar to the human IMPDH1 retinal variant and shares a reduced sensitivity to GTP-mediated inhibition. We also demonstrated that Impdh1a forms prominent protein filaments in vitro and in vivo in both rod and cone photoreceptor cell bodies, synapses, and to a lesser degree, in outer segments. These filaments changed length and cellular distribution throughout the day consistent with diurnal changes in both mRNA and protein levels. The loss of Impdh1a resulted in a substantial reduction of guanine levels, although cellular morphology and cGMP levels remained normal. Our findings demonstrate a significant role for IMPDH1 in photoreceptor guanine production and provide fundamental new information on the details of this protein in the zebrafish retina.
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Registered trials
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