{
  "abstract": "Nicotinic acetylcholine receptors (nAChRs) are primary targets of insecticides. While most mammalian nAChRs form functional channels in heterologous systems, insect nAChRs remain notoriously difficult to reconstitute. Here, we co-expressed insect/human subunit chimeras to enable functional analysis of heteromeric insect nAChR ligand‑binding sites in Xenopus laevis oocytes. First, EGFP-tagged human/cockroach α7 chimeras (Hα7/Pα7) were generated by exchanging the signal peptide (SP), extracellular (ECD), transmembrane (TMD), and intracellular (L3-4) domains. While all constructs were translated into protein, Hα7-like acetylcholine-evoked currents were only observed when human N- and C-terminal ECD and ICD were present, indicating that these domains impose insect-specific constraints on homomeric nAChR formation. Second, we generated heteromeric chimeric receptors by fusing insect-derived ECDs onto hα7 subunits. Co-expression of Pα6/Hα7L3-4 and Pα7ECD/Hα7 chimeras resulted in current amplitudes < 1 µA. Co-expression of the respective bee Aα5ECD/Hα7, Aα6ECD/Hα7, and Aα7ECD, CT/Hα7 chimeras yielded currents > 1 µA. α-Bungarotoxin inhibited diheteromeric Pα6α7 chimeras (IC₅₀ 49 nM) and triheteromeric Aα5/α6/α7 chimeras (IC₅₀ 51.2 nM). Third, this approach was applied to cockroach Pα2 and Pβ1 subunits. Replacement of the Pα2 ICD and the Pβ1 TMD/ICD with homologous regions from Hα2 and Hβ2 subunits and co-expression with Pα1 resulted in a ~ 100-fold current increase (2.6 µA) compared to the wild‑type Pα1α2β1 receptor. The chimeric receptor was activated by neonicotinoids (EC₅₀ clothianidin: 24.1 nM, EC₅₀ thiacloprid: 13.6 nM) and α-bungarotoxin-sensitive (IC₅₀: 36.6 nM). In conclusion, we demonstrate that replacement of insect ICD or ICD and TMD enables formation of functional insect-like heteromeric nAChRs without co-expression of chaperones.",
  "abstract_shown": true,
  "affiliations": [
    "Walther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, LMU Munich, Munich, Germany."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "name": "Gonxhe Lokaj"
    },
    {
      "affs": [
        0
      ],
      "name": "Annette Nicke",
      "orcid": "0000-0001-6798-505X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/80nswt67etsx5.bib",
  "cited_by": 0,
  "doi": "10.1080/19336950.2026.2736911",
  "fulltext_url": "https://europepmc.org/articles/PMC13690283",
  "id": "80nswt67etsx5",
  "issns": [
    "1933-6950",
    "1933-6969"
  ],
  "landing_url": "https://europepmc.org/article/MED/42905803",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Nicotinic Acetylcholine Receptors Study"
    ]
  ],
  "openalex": "W7223157608",
  "pdf_url": "https://europepmc.org/articles/PMC13690283?pdf=render",
  "pmcid": "PMC13690283",
  "pmid": "42905803",
  "published": "2026-10-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/80nswt67etsx5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:53Z",
      "native_id": "MED:42905803",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42905803"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Nicotinic Acetylcholine Receptors Study",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Functional expression of heteromeric insect/human nicotinic acetylcholine receptor chimeras without accessory proteins.",
  "title_text": "Functional expression of heteromeric insect/human nicotinic acetylcholine receptor chimeras without accessory proteins.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:53Z",
  "url": "https://research.draconitic.com/paper/80nswt67etsx5",
  "venue": "Channels (Austin, Tex.)",
  "versions": []
}