PRPS polymerization influences lens fiber organization in zebrafish. Issue 8 (14th April 2020)

• Record Type: Journal Article
• Authors: Begovich, Kyle; Yelon, Deborah; Wilhelm, James E.
• Is Part Of: Developmental dynamics. Volume 249:Issue 8(2020)
• Page Start: 1018
• Page End: 1031
• Publication Date: 2020-04-14
• Subjects: actin -- lens fiber -- metabolic enzyme filaments -- PRPS -- retina; Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.173
• Languages: English
• ISSNs: 1058-8388

Abstract

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. Key Findings: Novel mutant alleles of zebrafish prps1a and prps1b provide new insight into the roles of PRPS activity during development. Mutation of prps1a alone is sufficient to cause abnormally small eye size. Mutants that fail to assemble PRPS filaments exhibit disorganization of the actin network in the lens fibers.