Drosophila TRPg is required in neuroendocrine cells for post-ingestive food selection
- Kookmin University, Republic of Korea
- Johns Hopkins University School of Medicine, United States
- University of California, Santa Barbara, United States
Abstract
The mechanism through which the brain senses the metabolic state, enabling an animal to regulate food consumption, and discriminate between nutritional and non-nutritional foods is a fundamental question. Flies choose the sweeter non-nutritive sugar, L-glucose, over the nutritive D-glucose if they are not starved. However, under starvation conditions, they switch their preference to D-glucose, and this occurs independent of peripheral taste neurons. Here, we found that eliminating the TRPγ channel impairs the ability of starved flies to choose D-glucose. This food selection depends on trpγ expression in neurosecretory cells in the brain that express Diuretic hormone 44 (DH44). Loss of trpγ increases feeding, alters the physiology of the crop, which is the fly stomach equivalent, and decreases intracellular sugars and glycogen levels. Moreover, survival of starved trpγ flies is reduced. Expression of trpγ in DH44 neurons reverses these deficits. These results highlight roles for TRPγ in coordinating feeding with the metabolic state through expression in DH44 neuroendocrine cells.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1-7, and Figure supplements 1-7.
Article and author information
Author details
Funding
National Institute on Deafness and Other Communication Disorders (DC007864)
- Craig Montell
National Institute of Allergy and Infectious Diseases (AI65575)
- Craig Montell
National Institute of Allergy and Infectious Diseases (AI169386)
- Craig Montell
National Research Foundation of Korea (NRF-2018R1A2B6004202)
- Youngseok Lee
National Research Foundation of Korea (NRF-2016R1D1A1B03931273)
- Youngseok Lee
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Dhakal et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,299
- views
-
- 330
- downloads
-
- 11
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Drosophila TRPg is required in neuroendocrine cells for post-ingestive food selection
eLife 11:e56726.
https://doi.org/10.7554/eLife.56726
Further reading
-
- Neuroscience
Sleep loss increases AMPA-synaptic strength and number in the neocortex. However, this is only part of the synaptic sleep loss response. We report an increased AMPA/NMDA EPSC ratio in frontal-cortical pyramidal neurons of layers 2–3. Silent synapses are absent, decreasing the plastic potential to convert silent NMDA to active AMPA synapses. These sleep loss changes are recovered by sleep. Sleep genes are enriched for synaptic shaping cellular components controlling glutamate synapse phenotype, overlap with autism risk genes, and are primarily observed in excitatory pyramidal neurons projecting intra-telencephalically. These genes are enriched with genes controlled by the transcription factor, MEF2c, and its repressor, HDAC4. Sleep genes can thus provide a framework within which motor learning and training occur mediated by the sleep-dependent oscillation of glutamate-synaptic phenotypes.
-
- Neuroscience
- Structural Biology and Molecular Biophysics
We present near-atomic-resolution cryoEM structures of the mammalian voltage-gated potassium channel Kv1.2 in open, C-type inactivated, toxin-blocked and sodium-bound states at 3.2 Å, 2.5 Å, 3.2 Å, and 2.9 Å. These structures, all obtained at nominally zero membrane potential in detergent micelles, reveal distinct ion-occupancy patterns in the selectivity filter. The first two structures are very similar to those reported in the related Shaker channel and the much-studied Kv1.2–2.1 chimeric channel. On the other hand, two new structures show unexpected patterns of ion occupancy. First, the toxin α-Dendrotoxin, like Charybdotoxin, is seen to attach to the negatively-charged channel outer mouth, and a lysine residue penetrates into the selectivity filter, with the terminal amine coordinated by carbonyls, partially disrupting the outermost ion-binding site. In the remainder of the filter two densities of bound ions are observed, rather than three as observed with other toxin-blocked Kv channels. Second, a structure of Kv1.2 in Na+ solution does not show collapse or destabilization of the selectivity filter, but instead shows an intact selectivity filter with ion density in each binding site. We also attempted to image the C-type inactivated Kv1.2 W366F channel in Na+ solution, but the protein conformation was seen to be highly variable and only a low-resolution structure could be obtained. These findings present new insights into the stability of the selectivity filter and the mechanism of toxin block of this intensively studied, voltage-gated potassium channel.
