Subdued, a TMEM16 family Ca(2+)-activated Cl(−) channel in Drosophila melanogaster with an unexpected role in host defense

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, S...

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Detalles Bibliográficos
Autores principales: Wong, Xiu Ming, Younger, Susan, Peters, Christian J, Jan, Yuh Nung, Jan, Lily Y
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2013
Materias:
Biophysics and Structural Biology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814000/
https://www.ncbi.nlm.nih.gov/pubmed/24192034
http://dx.doi.org/10.7554/eLife.00862
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author Wong, Xiu Ming
Younger, Susan
Peters, Christian J
Jan, Yuh Nung
Jan, Lily Y
author_facet Wong, Xiu Ming
Younger, Susan
Peters, Christian J
Jan, Yuh Nung
Jan, Lily Y
author_sort Wong, Xiu Ming
collection PubMed
description 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
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spelling pubmed-38140002013-11-06 Subdued, a TMEM16 family Ca(2+)-activated Cl(−) channel in Drosophila melanogaster with an unexpected role in host defense Wong, Xiu Ming Younger, Susan Peters, Christian J Jan, Yuh Nung Jan, Lily Y eLife Biophysics and Structural Biology 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 eLife Sciences Publications, Ltd 2013-11-05 /pmc/articles/PMC3814000/ /pubmed/24192034 http://dx.doi.org/10.7554/eLife.00862 Text en Copyright © 2013, Wong et al http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biophysics and Structural Biology
Wong, Xiu Ming
Younger, Susan
Peters, Christian J
Jan, Yuh Nung
Jan, Lily Y
Subdued, a TMEM16 family Ca(2+)-activated Cl(−) channel in Drosophila melanogaster with an unexpected role in host defense
title Subdued, a TMEM16 family Ca(2+)-activated Cl(−) channel in Drosophila melanogaster with an unexpected role in host defense
title_full Subdued, a TMEM16 family Ca(2+)-activated Cl(−) channel in Drosophila melanogaster with an unexpected role in host defense
title_fullStr Subdued, a TMEM16 family Ca(2+)-activated Cl(−) channel in Drosophila melanogaster with an unexpected role in host defense
title_full_unstemmed Subdued, a TMEM16 family Ca(2+)-activated Cl(−) channel in Drosophila melanogaster with an unexpected role in host defense
title_short Subdued, a TMEM16 family Ca(2+)-activated Cl(−) channel in Drosophila melanogaster with an unexpected role in host defense
title_sort subdued, a tmem16 family ca(2+)-activated cl(−) channel in drosophila melanogaster with an unexpected role in host defense
topic Biophysics and Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814000/
https://www.ncbi.nlm.nih.gov/pubmed/24192034
http://dx.doi.org/10.7554/eLife.00862
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