PRPS Polymerization Influences Lens Fiber Organization in Zebrafish

Overview

Journal Dev Dyn

Publisher Wiley

Specialty Anatomy & Histology

Date 2020 Apr 4

PMID 32243675

Citations 10

Authors

Kyle Begovich

Deborah Yelon

James E Wilhelm

Affiliations

Soon will be listed here.

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.

Citing Articles

Inborn Errors of Purine Salvage and Catabolism.

Camici M, Garcia-Gil M, Allegrini S, Pesi R, Bernardini G, Micheli V Metabolites. 2023; 13(7).

PMID: 37512494 PMC: 10383617. DOI: 10.3390/metabo13070787.

Structural basis of human PRPS2 filaments.

Lu G, Hu H, Chang C, Zhong J, Zhou X, Guo C Cell Biosci. 2023; 13(1):100.

PMID: 37248548 PMC: 10227994. DOI: 10.1186/s13578-023-01037-z.

Human PRPS1 filaments stabilize allosteric sites to regulate activity.

Hvorecny K, Hargett K, Quispe J, Kollman J Nat Struct Mol Biol. 2023; 30(3):391-402.

PMID: 36747094 PMC: 10033377. DOI: 10.1038/s41594-023-00921-z.

Greater than the sum of parts: Mechanisms of metabolic regulation by enzyme filaments.

Hvorecny K, Kollman J Curr Opin Struct Biol. 2023; 79:102530.

PMID: 36709625 PMC: 10023394. DOI: 10.1016/j.sbi.2023.102530.

CTP synthase: the hissing of the cellular serpent.

Thangadurai S, Bajgiran M, Manickam S, Mohana-Kumaran N, Azzam G Histochem Cell Biol. 2022; 158(6):517-534.

PMID: 35881195 PMC: 9314535. DOI: 10.1007/s00418-022-02133-w.

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