Modulation of Drosophila post-feeding physiology and behavior by the neuropeptide leucokinin

Abstract

Behavior and physiology are orchestrated by neuropeptides acting as central neuromodulators and circulating hormones. An outstanding question is how these neuropeptides function to coordinate complex and competing behaviors. In Drosophila, the neuropeptide leucokinin (LK) modulates diverse functions, but mechanisms underlying these complex interactions remain poorly understood. As a first step towards understanding these mechanisms, we delineated LK circuitry that governs various aspects of post-feeding physiology and behavior. We found that impaired LK signaling in Lk and Lk receptor (Lkr) mutants affects diverse but coordinated processes, including regulation of stress, water homeostasis, feeding, locomotor activity, and metabolic rate. Next, we sought to define the populations of LK neurons that contribute to the different aspects of this physiology. We find that the calcium activity in abdominal ganglia LK neurons (ABLKs), but not in the two sets of brain neurons, increases specifically following water consumption, suggesting that ABLKs regulate water homeostasis and its associated physiology. To identify targets of LK peptide, we mapped the distribution of Lkr expression, mined a brain single-cell transcriptome dataset for genes coexpressed with Lkr, and identified synaptic partners of LK neurons. Lkr expression in the brain insulin-producing cells (IPCs), gut, renal tubules and chemosensory cells, correlates well with regulatory roles detected in the Lk and Lkr mutants. Furthermore, these mutants and flies with targeted knockdown of Lkr in IPCs displayed altered expression of insulin-like peptides (DILPs) and transcripts in IPCs and increased starvation resistance. Thus, some effects of LK signaling appear to occur via DILP action. Collectively, our data suggest that the three sets of LK neurons have different targets, but modulate the establishment of post-prandial homeostasis by regulating distinct physiological processes and behaviors such as diuresis, metabolism, organismal activity and insulin signaling. These findings provide a platform for investigating feeding-related neuroendocrine regulation of vital behavior and physiology.

A neuroendocrine pathway modulating osmotic stress inDrosophila

“…In the vinegar fly Drosophila melanogaster, several peptide hormones and neuropeptides have been shown to influence responses to nutrient and osmotic stress via actions on peripheral tissues such as the liver-like fat body and Malpighian (renal) tubules that are analogous to the mammalian kidneys. These hormones include Drosophila insulin-like peptides (DILPs), adipokinetic hormone (AKH), corazonin (Crz), leucokinin, diuretic hormone 44 (DH44) and capability gene-derived CAPA peptides [1][2][3][4][5][6][7][8][9][10][11][12]. In mammals, the hypothalamic-pituitary-adrenal (HPA) axis coordinates stress responses via the sequential secretion of corticotropinreleasing factor (CRF), adrenocorticotropic hormone (ACTH) and cortisol [13][14][15].…”

Neuropeptides in modulation of Drosophila behavior: how to get a grip on their pleiotropic actions

“…Leucokinin. In Drosophila, LK induces secretion in renal tubules in vitro, as well as regulates clock output, metabolism-related sleep, acute feeding, water balance, and plays roles in modulating tolerance to desiccation and ionic stress [2,[41][42][43][44][45][46]. There are two pairs of LK producing brain neurons, LHLK and SELK, and 11 pairs of neurosecretory cells, ABLK, in the TAG (Fig.…”

“…4). A few recent studies have sought to determine the functions of each of these three groups of cells [2,45,47].…”

“…While the ABLKs, but not brain neurons, are associated with regulation of water balance and responses to desiccation [45], the question is what are the roles of LHLKs and SELKs. The LHLKs are associated with the effects of LK signaling in regulation of locomotor activity, sleep and metabolism [2], whereas the subesophageal SELKs may be responsible for modulation of acute food ingestion (see [41,45]). Some of the effects of LK signaling are indirect via action on the brain IPCs, which express the LK receptor, LKR [2,45].…”

“…The LHLKs are associated with the effects of LK signaling in regulation of locomotor activity, sleep and metabolism [2], whereas the subesophageal SELKs may be responsible for modulation of acute food ingestion (see [41,45]). Some of the effects of LK signaling are indirect via action on the brain IPCs, which express the LK receptor, LKR [2,45]. The LHLKs are essential for starvation-mediated changes in sleep and it was shown that LKR expression in IPCs is required for mediating this phenotype [2].…”