The taste of ribonucleosides: Novel macronutrients essential for larval growth are sensed by Drosophila gustatory receptor proteins

Abstract

Animals employ various types of taste receptors to identify and discriminate between different nutritious food chemicals. These macronutrients are thought to fall into 3 major groups: carbohydrates/sugars, proteins/amino acids, and fats. Here, we report that Drosophila larvae exhibit a novel appetitive feeding behavior towards ribose, ribonucleosides, and RNA. We identified members of the gustatory receptor (Gr) subfamily 28 (Gr28), expressed in both external and internal chemosensory neurons as molecular receptors necessary for cellular and appetitive behavioral responses to ribonucleosides and RNA. Specifically, behavioral preference assays show that larvae are strongly attracted to ribose- or RNA-containing agarose in a Gr28-dependent manner. Moreover, Ca2+ imaging experiments reveal that Gr28a-expressing taste neurons are activated by ribose, RNA and some ribonucleosides and that these responses can be conveyed to Gr43aGAL4 fructose-sensing neurons by expressing single members of the Gr28 gene family. Lastly, we establish a critical role in behavioral fitness for the Gr28 genes by showing that Gr28 mutant larvae exhibit low survival rates when challenged to find ribonucleosides in food. Together, our work identifies a novel taste modality dedicated to the detection of RNA and ribonucleosides, nutrients that are essential for survival during the accelerated growth phase of Drosophila larvae.

Metabolic cooperation among commensal bacteria supportsDrosophilajuvenile growth under nutritional stress

“…Lactate supplementation to Acetobacter species triggers the release of metabolic by-products that include ribonucleotides AMP, GMP and UMP, vitamin and amino-acid derivatives: SAM, SAH, NAD+, FMN 575 and pyridoxamine phosphate, which are co-factors for enzymes involved in multiple host metabolic pathways. These metabolites are essential for optimal larval growth and survival (Consuegra et al, 2020;Mishra et al, 2018;Sang, 1956). Fatty acids and membrane lipids are another group of metabolites whose production is enhanced by lactate presence.…”

“…Here, using Drosophila bi-associated with A. pomorum and L. plantarum, we characterized the metabolic dialogues among the three partners in a strictly controlled nutritional environment low in amino acids to mimic chronic protein undernutrition, 95 namely a fully chemically-defined or holidic diet (HD) . HDs support suboptimal growth and development of Drosophila larvae (Jang and Lee, 2018;Piper et al, 2013;Rapport et al, 1983;Schultz et al, 1946) yet it has proved to be a useful tool to study the specific influence of individual nutrients on Drosophila physiology (Jang and Lee, 2018;Mishra et al, 2018;Piper et al, 2013Piper et al, , 2017. This experimental 100 model grants us complete control over 3 key parameters in the system: the diet, the host and its commensal partners.…”

Drosophila-associated bacteria differentially shape the nutritional requirements of their host during juvenile growth

“…The first development of HDs supporting the growth of Drosophila can be traced back to the 1940s [37], and they were used to assess the direct impact of the nutritional environment on axenic larvae in the 1950s [38,39]. HDs were then used to investigate the links between nutrition and life span [40][41][42][43], fecundity [40][41][42]44], food choice behavior [45,46], nutrient sensing [47], and growth and maturation [33,[40][41][42][48][49][50]. In this study, we adopted the recently developed fly exome-matched amino acid ratio (FLYAA) HD in which the amino acid concentrations are calculated so that they match the amino acid ratios found in the translated exome of the fly [40].…”

The Taste of Blood in Mosquitoes

“…Similarly, there is no description of the taste of ATP. The closest comparison to ATP detection is in mammals, where specific 5'-monophosphate nucleotides potentiate umami perception (Yamaguchi, 1967) and in Drosophila melanogaster larvae, where certain ribonucleosides directly activate Gr28-expressing taste neurons (Mishra et al, 2018). Our work shows that the taste of blood is multidimensional and that multiple taste qualities, both canonical and noncanonical, are integrated across subsets of bloodsensitive neurons and for the particular subset of Integrator neurons, within individual neurons.…”