人巨噬细胞 C 型凝集素与 Mincle 形成异源二聚体受体复合物,但不与 Dectin-2 形成。

Human macrophage C-type lectin forms a heteromeric receptor complex with Mincle but not Dectin-2.

机构信息

Division of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

出版信息

Scand J Immunol. 2022 May;95(5):e13149. doi: 10.1111/sji.13149. Epub 2022 Feb 27.

Abstract

MCL, Mincle and Dectin-2 are C-type lectin receptors expressed by subsets of myeloid cells, and their genes cluster together in the APLEC/Dectin-2 gene complex. We have previously shown that MCL and Mincle form a heterodimer in the rat, and others have shown that MCL and Dectin-2 form a heterodimer in the mouse. In the rat, Dectin-2 is a pseudogene, but here, we examine the association of the three receptors in human. In co-transfection experiments analyzed with flow cytometry and immunoprecipitation, we here show that human MCL and Mincle form a disulphide-linked heterodimer that associates with the signalling adaptor molecule FcεRIγ, in accordance with our previous findings in the rat. In contrast to previous findings in the rat, data in this paper indicate a direct association of MCL with FcεRIγ, as previously shown for mouse MCL. We were unable to demonstrate the formation of a heterodimer between human MCL and Dectin-2. Thus, despite similarities, there may be important differences in the conformation of these receptors between rat, mouse and human, and this may have functional consequences.

摘要

MCL、Mincle 和 Dectin-2 是表达在髓样细胞亚群中的 C 型凝集素受体,它们的基因聚集在 APLEC/Dectin-2 基因复合物中。我们之前已经表明,MCL 和 Mincle 在大鼠中形成异二聚体,其他人已经表明,MCL 和 Dectin-2 在小鼠中形成异二聚体。在大鼠中,Dectin-2 是一个假基因,但在这里,我们研究了三种受体在人类中的关联。在通过流式细胞术和免疫沉淀分析的共转染实验中,我们在此表明,人类 MCL 和 Mincle 形成二硫键连接的异二聚体,与信号转导衔接子分子 FcεRIγ 结合,这与我们在大鼠中的先前发现一致。与大鼠中的先前发现相反,本文中的数据表明 MCL 与 FcεRIγ 之间存在直接关联,如先前在小鼠中显示的那样。我们无法证明人 MCL 和 Dectin-2 之间形成异二聚体。因此,尽管存在相似之处,但这些受体在大鼠、小鼠和人类之间的构象可能存在重要差异,这可能具有功能后果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2f9/10234441/a01191fe981d/SJI-95-e13149-g004.jpg

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