Multiple combinations of RDL subunits diversify the repertoire of GABA receptors in the honey bee parasite Varroa destructor.

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Title: Multiple combinations of RDL subunits diversify the repertoire of GABA receptors in the honey bee parasite Varroa destructor.
Authors: Ménard, Claudine1, Folacci, Mathilde1, Brunello, Lorène1, Charreton, Mercedes2, Collet, Claude2, Mary, Rosanna1, Rousset, Matthieu1, Thibaud, Jean-Baptiste1, Vignes, Michel1, Charnet, Pierre1, Cens, Thierry1 thierry.cens@inserm.fr
Source: Journal of Biological Chemistry. 12/7/2018, Vol. 293 Issue 49, p19012-19024. 13p.
Subjects: Varroa destructor, Honeybees, Neurotransmitters, Cationic lipids, Ectoparasites
Abstract: In insects, γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter, and GABA-gated ion channels are the target of different classes of insecticides, including fipronil. We report here the cloning of six subunits (four RDL, one LCCH3, and one GRD) that constitute the repertoire of the GABA-gated ion channel family of the Varroa mite (Varroa destructor), a honey bee ectoparasite. We also isolated a truncated GRD subunit with a premature stop codon. We found that when expressed in Xenopus laevis oocytes, three of the four RDL subunits (VdesRDL1, VdesRDL2, and VdesRDL3) formed functional, homomultimeric anionic receptors, whereas GRD and LCCH3 produced heteromultimeric cationic receptors. These receptors displayed specific sensitivities toward GABA and fipronil, and VdesRDL1 was the most resistant to the insecticide. We identified specific residues in the VdesRDL1 pore-lining region that explain its high resistance to fipronil. VdesRDL4 did not form a functional receptor when expressed alone, but it assembled with VdesRDL1 to form a heteromultimeric receptor with properties distinct from those of the VdesRDL1 homomultimeric receptor. Moreover, VdesRDL1 physically interacted with VdesRDL3, generating a heteromultimeric receptor combining properties of both subunits. On the other hand, we did not detect any functional interaction between VdesLCCH3 and the VdesRDL subunits, an observation that differed from what was previously reported for Drosophila melanogaster. In conclusion, this study provides insights relevant to improve our understanding of the precise role of GABAergic signaling in insects and new tools for the development of Varroa mite-specific insecticidal agents that do not harm honey bees. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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Items – Name: Title
  Label: Title
  Group: Ti
  Data: Multiple combinations of RDL subunits diversify the repertoire of GABA receptors in the honey bee parasite Varroa destructor.
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  Data: <searchLink fieldCode="AR" term="%22Ménard%2C+Claudine%22">Ménard, Claudine</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Folacci%2C+Mathilde%22">Folacci, Mathilde</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Brunello%2C+Lorène%22">Brunello, Lorène</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Charreton%2C+Mercedes%22">Charreton, Mercedes</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Collet%2C+Claude%22">Collet, Claude</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Mary%2C+Rosanna%22">Mary, Rosanna</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Rousset%2C+Matthieu%22">Rousset, Matthieu</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Thibaud%2C+Jean-Baptiste%22">Thibaud, Jean-Baptiste</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Vignes%2C+Michel%22">Vignes, Michel</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Charnet%2C+Pierre%22">Charnet, Pierre</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Cens%2C+Thierry%22">Cens, Thierry</searchLink><relatesTo>1</relatesTo><i> thierry.cens@inserm.fr</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 12/7/2018, Vol. 293 Issue 49, p19012-19024. 13p.
– Name: Subject
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  Data: <searchLink fieldCode="DE" term="%22Varroa+destructor%22">Varroa destructor</searchLink><br /><searchLink fieldCode="DE" term="%22Honeybees%22">Honeybees</searchLink><br /><searchLink fieldCode="DE" term="%22Neurotransmitters%22">Neurotransmitters</searchLink><br /><searchLink fieldCode="DE" term="%22Cationic+lipids%22">Cationic lipids</searchLink><br /><searchLink fieldCode="DE" term="%22Ectoparasites%22">Ectoparasites</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: In insects, γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter, and GABA-gated ion channels are the target of different classes of insecticides, including fipronil. We report here the cloning of six subunits (four RDL, one LCCH3, and one GRD) that constitute the repertoire of the GABA-gated ion channel family of the Varroa mite (Varroa destructor), a honey bee ectoparasite. We also isolated a truncated GRD subunit with a premature stop codon. We found that when expressed in Xenopus laevis oocytes, three of the four RDL subunits (VdesRDL1, VdesRDL2, and VdesRDL3) formed functional, homomultimeric anionic receptors, whereas GRD and LCCH3 produced heteromultimeric cationic receptors. These receptors displayed specific sensitivities toward GABA and fipronil, and VdesRDL1 was the most resistant to the insecticide. We identified specific residues in the VdesRDL1 pore-lining region that explain its high resistance to fipronil. VdesRDL4 did not form a functional receptor when expressed alone, but it assembled with VdesRDL1 to form a heteromultimeric receptor with properties distinct from those of the VdesRDL1 homomultimeric receptor. Moreover, VdesRDL1 physically interacted with VdesRDL3, generating a heteromultimeric receptor combining properties of both subunits. On the other hand, we did not detect any functional interaction between VdesLCCH3 and the VdesRDL subunits, an observation that differed from what was previously reported for Drosophila melanogaster. In conclusion, this study provides insights relevant to improve our understanding of the precise role of GABAergic signaling in insects and new tools for the development of Varroa mite-specific insecticidal agents that do not harm honey bees. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1074/jbc.RA118.005365
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      – Code: eng
        Text: English
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        PageCount: 13
        StartPage: 19012
    Subjects:
      – SubjectFull: Varroa destructor
        Type: general
      – SubjectFull: Honeybees
        Type: general
      – SubjectFull: Neurotransmitters
        Type: general
      – SubjectFull: Cationic lipids
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      – SubjectFull: Ectoparasites
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      – TitleFull: Multiple combinations of RDL subunits diversify the repertoire of GABA receptors in the honey bee parasite Varroa destructor.
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              Text: 12/7/2018
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