Molecular and functional in vivo characterisation of murine Dectin‐1 isoforms

Abstract: Dectin‐1 is a C‐type lectin‐receptor involved in sensing fungi by innate immune cells. Encoded by the Clec7a gene, Dectin‐1 exists in two major splice isoforms, Dectin‐1a and 1b, which differ in the presence of a membrane‐proximal stalk domain. As reported previously, this domain determines degradative routes for Dectin‐1a and 1b leading to the generation of a stable N‐terminal fragment exclusively from Dectin‐1a. Here, we narrow down the responsible part of the stalk and demonstrate the stabilisation of the Dectin‐1a N‐terminal fragment in tetraspanin‐enriched microdomains. C57BL/6 and BALB/c mice show divergent Dectin‐1 isoform expression patterns, which are caused by a single nucleotide polymorphism in exon 3 of the Clec7a gene, leading to a non‐sense Dectin‐1a mRNA in C57BL/6 mice. Using backcrossing, we generated mice with the C57BL/6 Clec7a allele on a BALB/c background and compared these to the parental strains. Expression of the C57BL/6 allele leads to the exclusive presence of the Dectin‐1b protein. Furthermore, it was associated with higher Dectin‐1 mRNA expression, but less Dectin‐1 at the cell surface according to flow cytometry. In neutrophils, this altered ROS production induced by Dectin‐1 model ligands, while cellular responses in macrophages and dendritic cells were not significantly influenced by the Dectin‐1 isoform pattern.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Molecular and functional in vivo characterisation of murine Dectin‐1 isoforms ; day:28 ; month:08 ; year:2024 ; extent:22
European journal of immunology ; (28.08.2024) (gesamt 22)

Urheber
Leinung, Nadja
Mentrup, Torben
Hodzic, Sajma
Schröder, Bernd

DOI
10.1002/eji.202451092
URN
urn:nbn:de:101:1-2408291406177.742197068415
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:33 MESZ

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Beteiligte

  • Leinung, Nadja
  • Mentrup, Torben
  • Hodzic, Sajma
  • Schröder, Bernd

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