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Neuronal expression in Drosophila of an evolutionarily conserved metallophosphodiesterase reveals pleiotropic roles in longevity and odorant response

Gupta, K and Chakrabarti, S and Janardan, V and Gogia, N and Banerjee, S and Srinivas, S and Mahishi, D and Visweswariah, SS (2023) Neuronal expression in Drosophila of an evolutionarily conserved metallophosphodiesterase reveals pleiotropic roles in longevity and odorant response. In: PLoS Genetics, 19 (9).

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Official URL: https://doi.org/10.1371/journal.pgen.1010962


Evolutionarily conserved genes often play critical roles in organismal physiology. Here, we describe multiple roles of a previously uncharacterized Class III metallophosphodiesterase in Drosophila, an ortholog of the MPPED1 and MPPED2 proteins expressed in the mammalian brain. dMpped, the product of CG16717, hydrolyzed phosphodiester substrates including cAMP and cGMP in a metal-dependent manner. dMpped is expressed during development and in the adult fly. RNA-seq analysis of dMppedKO flies revealed misregulation of innate immune pathways. dMppedKO flies showed a reduced lifespan, which could be restored in Dredd hypomorphs, indicating that excessive production of antimicrobial peptides contributed to reduced longevity. Elevated levels of cAMP and cGMP in the brain of dMppedKO flies was restored on neuronal expression of dMpped, with a concomitant reduction in levels of antimicrobial peptides and restoration of normal life span. We observed that dMpped is expressed in the antennal lobe in the fly brain. dMppedKO flies showed defective specific attractant perception and desiccation sensitivity, correlated with the overexpression of Obp28 and Obp59 in knock-out flies. Importantly, neuronal expression of mammalian MPPED2 restored lifespan in dMppedKO flies. This is the first description of the pleiotropic roles of an evolutionarily conserved metallophosphodiesterase that may moonlight in diverse signaling pathways in an organism. Copyright: © 2023 Gupta et al.

Item Type: Journal Article
Publication: PLoS Genetics
Publisher: Public Library of Science
Additional Information: The copyright for this article belongs to the Authors.
Keywords: fragrance; metallophosphodiesterase; phosphodiesterase; polypeptide antibiotic agent; unclassified drug; Drosophila protein, Article; Drosophila; Drosophila melanogaster; false discovery rate; female; immunofluorescence; innate immunity; longevity; mutagenesis; nonhuman; polyacrylamide gel electrophoresis; real time polymerase chain reaction; RNA sequence; signal transduction; synaptic transmission; Western blotting; Y-maze test; animal; genetics; mammal; metabolism, Animals; Antimicrobial Peptides; Drosophila; Drosophila melanogaster; Drosophila Proteins; Longevity; Mammals; Odorants
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited: 14 Dec 2023 04:36
Last Modified: 14 Dec 2023 04:36
URI: https://eprints.iisc.ac.in/id/eprint/83412

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