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Development of a fly model to probe the functions of inorganic polyphosphates


Authors:
Sunayana Sarkar 1; Harsha Sharma 1; Jayashree Suresh Ladke 2; Rashna Bhandari 2; Manish Jaiswal 1

Affiliations:
1) TATA Institute of Fundamental Research, Hyderabad, India; 2) Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India

Keywords:
e. gene targeting and modification; e. neuronal morphogenesis

Inorganic polyphosphate (polyP), which consists of chains of orthophosphate residues of varying chain lengths, is found in all living organisms alongside other phosphate-rich biomolecules such as ATP and inositol phosphates. The biological functions of polyP have been extensively studied in prokaryotes and unicellular eukaryotes, however, their functions in metazoans are largely underexplored. In fact, polyP has been referred to as a molecular fossil. In recent years polyP has been shown to be implicated largely in blood clotting and bone mineralisation in mammals. Moreover, several other functions of polyP are predicted due to its presence in various cell types and its specific binding with numerous proteins. However, the major limitation in testing the functions of polyP in metazoans is the elusivity of the genes involved in polyP synthesis and turnover, which restricts modulation of polyP levels in vivo. We have developed a Drosophila model to study the functions of polyP. Here we show that polyP exists in flies and that its levels are developmentally regulated during embryogenesis. Further, through phylogenetic analysis, we characterised Prune as a putative exopolyphosphatase. Indeed, we observed significantly higher levels of polyP in prune mutants as compared to wildtype flies. Prune is a mitochondrial protein known to hydrolyze cAMP. Mutations in prune are linked to a variety of processes such as mitochondrial biogenesis, eye pigmentation and neurodegeneration. Based on our data, we surmise that prune mediated regulation of polyP may attribute to some of the prune phenotypes and will help understand polyP biology in metazoans.