title: Drosophila SLC5A11 Mediates Hunger by Regulating K(+) Channel Activity.
abstract: Hunger is a powerful drive that stimulates food intake. Yet, the mechanism that determines how the energy deficits that result in hunger are represented in the brain and promote feeding is not well understood. We previously described SLC5A11-a sodium/solute co-transporter-like-(or cupcake) in Drosophila melanogaster, which is required for the fly to select a nutritive sugar over a sweeter nonnutritive sugar after periods of food deprivation. SLC5A11 acts on approximately 12 pairs of ellipsoid body (EB) R4 neurons to trigger the selection of nutritive sugars, but the underlying mechanism is not understood. Here, we report that the excitability of SLC5A11-expressing EB R4 neurons increases dramatically during starvation and that this increase is abolished in the SLC5A11 mutation. Artificial activation of SLC5A11-expresssing neurons is sufficient to promote feeding and hunger-driven behaviors; silencing these neurons has the opposite effect. Notably, SLC5A11 transcript levels in the brain increase significantly when flies are starved and decrease shortly after starved flies are refed. Furthermore, expression of SLC5A11 is sufficient for promoting hunger-driven behaviors and enhancing the excitability of SLC5A11-expressing neurons. SLC5A11 inhibits the function of the Drosophila KCNQ potassium channel in a heterologous expression system. Accordingly, a knockdown of dKCNQ expression in SLC5A11-expressing neurons produces hunger-driven behaviors even in fed flies, mimicking the overexpression of SLC5A11. We propose that starvation increases SLC5A11 expression, which enhances the excitability of SLC5A11-expressing neurons by suppressing dKCNQ channels, thereby conferring the hunger state.
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA; Neuroscience Institute, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
authors.forename: Jin-Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA; Neuroscience Institute, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Dus
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
authors.forename: Seonil
authors.initials: S
authors.lastname: Kim
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA; Neuroscience Institute, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
authors.forename: Farhan
authors.initials: F
authors.lastname: Abu
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA; Neuroscience Institute, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
authors.forename: Makoto I
authors.initials: MI
authors.lastname: Kanai
authors.affiliation: Neuroscience Institute, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA; Department of Physiology and Neuroscience , New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Rudy
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA; Neuroscience Institute, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA. Electronic address: greg.suh@med.nyu.edu.
authors.forename: Greg S B
authors.initials: GSB
authors.lastname: Suh
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D005508:Food Deprivation; D006815:Hunger; D008297:Male; D009474:Neurons / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D051247:Sodium-Glucose Transport Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D015221:Potassium Channels; C581906:SLC5A11 protein, Drosophila; D051247:Sodium-Glucose Transport Proteins