Opposing GPCR signaling programs protein intake setpoint in Drosophila.

GPCR signaling RFamide homeostasis motivated behavior protein intake setpoint resting membrane potential

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
20 Aug 2024
Historique:
received: 30 06 2023
revised: 31 05 2024
accepted: 25 07 2024
medline: 31 8 2024
pubmed: 31 8 2024
entrez: 28 8 2024
Statut: aheadofprint

Résumé

Animals defend a target level for their fundamental needs, including food, water, and sleep. Deviation from the target range, or "setpoint," triggers motivated behaviors to eliminate that difference. Whether and how the setpoint itself is encoded remains enigmatic for all motivated behaviors. Employing a high-throughput feeding assay in Drosophila, we demonstrate that the protein intake setpoint is set to different values in male, virgin female, and mated female flies to meet their varying protein demands. Leveraging this setpoint variability, we found, remarkably, that the information on the intake setpoint is stored within the protein hunger neurons as the resting membrane potential. Two RFamide G protein-coupled receptor (GPCR) pathways, by tuning the resting membrane potential in opposite directions, coordinately program and adjust the protein intake setpoint. Together, our studies map the protein intake setpoint to a single trackable physiological parameter and elucidate the cellular and molecular mechanisms underlying setpoint determination and modulation.

Identifiants

DOI: 10.1016/j.cell.2024.07.047 PMID: 39197448
pubmed: 39197448
pii: S0092-8674(24)00841-9
doi: 10.1016/j.cell.2024.07.047
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Guangyan Wu (G)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.

Tianji Ma (T)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.

Clare E Hancock (CE)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.

Santiago Gonzalez (S)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.

Binod Aryal (B)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.

Sharon Vaz (S)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.

Gabrielle Chan (G)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.

Madison Palarca-Wong (M)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.

Nick Allen (N)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA.

Chan-I Chung (CI)

Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.

Xiaokun Shu (X)

Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.

Qili Liu (Q)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94158, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: qili.liu@ucsf.edu.

Classifications MeSH