DH44 neurons: gut-brain amino acid sensors

Chen, Yu-Chieh; Dahanukar, Anupama

doi:10.1038/s41422-018-0101-z

Cited by 7 publications

(4 citation statements)

References 9 publications

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“…To further dissect the PI neurons for functional involvement in ppGpp regulation of sleep, we tested Gal4 lines known to drive expression in PI neurons: Dh44-Gal4 (Cannell et al, 2016; Chen and Dahanukar, 2018), Dilp2-Gal4 (Crocker et al, 2010; Semaniuk et al, 2018; Yurgel et al, 2019) and R19G10-Gal4 (Collin et al, 2011; Ohno et al, 2017). To confirm whether mesh1 is expressed in the PI neurons labeled by these drivers, we generated a Flp line of mesh1 ( M1KIflp , Fig.…”

Section: Resultsmentioning

confidence: 99%

ppGpp is Present in and Functions to Regulate Sleep inDrosophila

Dai

Yang

Zhang

et al. 2022

Preprint

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Sleep is essential for animals, and receives inputs from circadian, homeostasis, and environment, yet the mechanisms of sleep regulation remain elusive. Discovery of molecules in living systems and demonstration of their functional roles are pivotal in furthering our understanding of the molecular basis of biology. Here we report that ppGpp (guanosine-5-diphosphate, 3-diphosphate), a molecule that has been detected in prokaryotes for more than five decades, is present inDrosophila, and plays an important role in regulation of sleep and SISL (starvation induced sleep loss). ppGpp is detected in germ-freeDrosophilaand hydrolyzed by an enzyme encoded by themesh1gene inDrosophila. Nighttime sleep and SISL were defected inmesh1mutant flies, and rescued by expression of wildtype Mesh1, but not the enzymatically defective mutant Mesh1E66A. Ectopic expression of RelA, theE. colisynthetase for ppGpp, phenocopiedmesh1knockout mutants, whereas overexpression of Mesh1 resulted in the opposite phenotypes, supporting that ppGpp is both necessary and sufficient in sleep regulation. A chemoconnectomic screen followed by genetic intersection experiments implicate the Dilp2 neurons in thepars intercerebralis(PI) brain region as the site of ppGpp function. Our results have thus supported that ppGpp is present in animals after long lag since its discovery in bacteria, and revealed a physiological role of ppGpp in sleep regulation for the first time.

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Section: Resultsmentioning

confidence: 99%

ppGpp is Present in and Functions to Regulate Sleep inDrosophila

Dai

Yang

Zhang

et al. 2022

Preprint

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“…To further dissect the PI neurons for functional involvement in ppGpp regulation of sleep, we tested five Gal4 lines known to drive expression in PI neurons: a line for PI (c767, Cavanaugh et al ., 2014; Donlea et al ., 2009), three lines for neuropeptides Dh44 (Cannel et al ., 2016; Chen and Dahanukar, 2018), Dilp2 (Crocker et al ., 2010; Semaniuk et al ., 2018; Yurgel et al ., 2019) and SIFa (Martelli et al ., 2017; Park et al ., 2014), and one line for receptor R19G10 (an RYamide receptor) (Collins et al ., 2011; Ohno et al ., 2017). We crossed each of these PI drivers to a line of knockin flies with in-frame fusion of the flippase gene to the C terminus of the mesh1 gene (M1KIflp) (Figure S4A), which was recombined with UAS-FRT-stop-FRT-mCD8-GFP as a reporter.…”

Section: Resultsmentioning

confidence: 99%

ppGpp Is Present in and Functions to Regulate Sleep in Drosophila

Young

Zhang

Daixi

et al. 2021

Preprint

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Discovery of molecules in living systems and demonstration of their functional roles are pivotal in furthering our understanding of the molecular basis of biology. ppGpp (guanosine-5’-diphosphate, 3’-diphosphate) has been detected in prokaryotes for more than five decades. Here we report that a genetic screen followed by chemical analysis revealed the presence of ppGpp in Drosophila.It can be detected in germ-free Drosophila and its level is controlled by an enzyme encoded by the mesh1 gene in Drosophila. Loss of function mutations in mesh1, which encoded the ppGpp degrading enzyme led to longer sleep latency and less total sleep. These phenotypes could be rescued by wild type mesh1, but not by the enzymatically defective mutant Mesh1E66A, functionally implicating ppGpp. Ectopic expression of RelA, the E. colisynthetase for ppGpp, phenocopied mesh1 knockout mutants, whereas overexpression of mesh1 resulted in the opposite phenotypes, supporting that ppGpp is both necessary and sufficient in sleep regulation. mesh1 is expressed in a specific population of neurons, and a chemoconnectomic screen followed by genetic intersection experiments implicate the pars intercerebralis (PI) as the site of ppGpp function. Our results have thus revealed that ppGpp is present in animals after long lag since its discovery in bacteria. Furthermore, we have demonstrated that ppGpp in a specific subset of neurons plays a physiological role in regulating sleep.

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Section: Taste-independent Sugar and Amino Acid Sensormentioning

confidence: 99%

“…DH44 + PI neurons are activated by circulating sugars and stimulated by several amino acids, including L-Glu, L-Ala, and L-Asp, which are supplied from food sources (40,43). DH44 + PI neurons are essential to increase the feeding amount which contains nutritive sugars and those three amino acids, L-Glu, L-Ala, and L-Asp (40,43). However, it is unclear whether detecting those three amino acids by DH44 + PI neurons would be necessary for shifting the food preference between carbohydrates and proteins in a protein-deprived condition.…”

Section: Taste-independent Sugar and Amino Acid Sensormentioning

confidence: 99%

The role of diuretic hormones (DHs) and their receptors in Drosophila

Lee

Jang

2023

BMB Rep

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Maintaining internal homeostasis and regulating innate behaviors are essential for animal survival. In various animal species, a highly conserved neuroendocrine system integrates sensory inputs and regulates physiological responses to environmental and internal changes. Diuretic hormones 44 and 31, which are homologs of mammalian corticotropin-releasing factor (CRF) and calcitonin gene-related peptide (CGRP), respectively, control body fluid secretion in Drosophila. These neuropeptides and their receptors have multiple physiological roles, including the regulation of body-fluid secretion, sleep:wake cycle, internal nutrientsensing, and CO2-dependent response. This review discusses the physiological and behavioral roles of DH44 and DH31 signaling pathways, consisting of neuroendocrine cells that secrete DH44 or DH31 peptides and their receptor-expressing organs. Further research is needed to understand the regulatory mechanisms of the behavioral processes mediated by these neuroendocrine systems. BMB Rep. www.bmbreports.org Invited Mini ReviewThe role of DHs and their receptors in Drosophila Gahbien Lee, et al.

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DH44 neurons: gut-brain amino acid sensors

Cited by 7 publications

References 9 publications

ppGpp is Present in and Functions to Regulate Sleep inDrosophila

ppGpp is Present in and Functions to Regulate Sleep inDrosophila

ppGpp Is Present in and Functions to Regulate Sleep in Drosophila

The role of diuretic hormones (DHs) and their receptors in Drosophila

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