title: Subdued, a TMEM16 family Ca²⁺-activated Cl⁻channel in Drosophila melanogaster with an unexpected role in host defense.
abstract: TMEM16A and TMEM16B are calcium-activated chloride channels (CaCCs) with important functions in mammalian physiology. Whether distant relatives of the vertebrate TMEM16 families also form CaCCs is an intriguing open question. Here we report that a TMEM16 family member from Drosophila melanogaster, Subdued (CG16718), is a CaCC. Amino acid substitutions of Subdued alter the ion selectivity and kinetic properties of the CaCC channels heterologously expressed in HEK 293T cells. This Drosophila channel displays characteristics of classic CaCCs, thereby providing evidence for evolutionarily conserved biophysical properties in the TMEM16 family. Additionally, we show that knockout flies lacking subdued gene activity more readily succumb to death caused by ingesting the pathogenic bacteria Serratia marcescens, suggesting that subdued has novel functions in Drosophila host defense. DOI: http://dx.doi.org/10.7554/eLife.00862.001.
authors.affiliation: Graduate Program in Chemistry and Chemical Biology, University of California, San Francisco, San Francisco, United States.
authors.forename: Xiu Ming
authors.initials: XM
authors.lastname: Wong
authors.forename: Susan
authors.initials: S
authors.lastname: Younger
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Peters
authors.forename: Yuh Nung
authors.initials: YN
authors.lastname: Jan
authors.forename: Lily Y
authors.initials: LY
authors.lastname: Jan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000502:physiology; D018118:Chloride Channels / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000378:metabolism*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
chemical_list: D002147:Calmodulin; D018118:Chloride Channels; D002118:Calcium
keywords: Drosophila host defense; TMEM16 family; calcium-activated chloride channels