PUBLICATION
Phosphoribosyl pyrophosphate synthetase polymerization influences lens fiber organization in zebrafish
- Authors
- Begovich, K., Yelon, D., Wilhelm, J.E.
- ID
- ZDB-PUB-200422-10
- Date
- 2020
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 249(8): 1018-1031 (Journal)
- Registered Authors
- Yelon, Deborah
- Keywords
- PRPS, actin, lens fiber, metabolic enzyme filaments, retina
- MeSH Terms
-
- Actins/metabolism
- Air Sacs/embryology
- Alleles
- Animals
- Eye/embryology
- Eye/growth & development
- Gene Expression Regulation, Developmental
- Genotype
- Lens, Crystalline/embryology*
- Lens, Crystalline/growth & development*
- Microscopy, Fluorescence
- Mutation
- Pigmentation
- Polymerization
- Retina/embryology
- Retinal Pigment Epithelium/embryology
- Ribose-Phosphate Pyrophosphokinase/genetics*
- Ribose-Phosphate Pyrophosphokinase/metabolism*
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism*
- PubMed
- 32243675 Full text @ Dev. Dyn.
Citation
Begovich, K., Yelon, D., Wilhelm, J.E. (2020) Phosphoribosyl pyrophosphate synthetase polymerization influences lens fiber organization in zebrafish. Developmental Dynamics : an official publication of the American Association of Anatomists. 249(8):1018-1031.
Abstract
Background The self-assembly of metabolic enzymes into filaments or foci highlights an intriguing mechanism for the regulation of metabolic activity. Recently, we identified the conserved polymerization of phosphoribosyl pyrophosphate synthetase (PRPS), which catalyzes the first step in purine nucleotide synthesis, in yeast and cultured mammalian cells. While previous work has revealed that loss of PRPS activity regulates retinal development in zebrafish, the extent to which PRPS filament formation affects tissue development remains unknown.
Results By generating novel alleles in the zebrafish PRPS paralogs, prps1a and prps1b, we gained new insight into the role of PRPS filaments during eye development. We found that mutations in prps1a alone are sufficient to generate abnormally small eyes along with defects in head size, pigmentation, and swim bladder inflation. Furthermore, a loss-of-function mutation that truncates the Prps1a protein resulted in the failure of PRPS filament assembly. Lastly, in mutants that fail to assemble PRPS filaments, we observed disorganization of the actin network in the lens fibers.
Conclusions The truncation of Prps1a blocked PRPS filament formation and resulted in a disorganized lens fiber actin network. Altogether, these findings highlight a potential role for PRPS filaments during lens fiber organization in zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping