Chemoattractant receptor signaling in humoral immunity.

IF 4.8 4区医学 Q2 IMMUNOLOGY International immunology Pub Date : 2024-04-04 DOI:10.1093/intimm/dxae021

Taiichiro Shirai, Akiko Nakai, Kazuhiro Suzuki

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Abstract

Efficient induction of humoral immune responses depends on orchestrated migration of B cells within lymphoid organs, which is governed by G protein-coupled receptors (GPCRs) responding to chemoattractants, represented by chemokines. After ligand binding, GPCRs are phosphorylated by different GPCR kinases (GRKs) at distinct sites on the receptor C termini, which dictates functional outcomes of β-arrestin-mediated signaling, ranging from receptor inactivation to effector molecule activation. However, the molecular mechanisms by which individual GRKs are selectively targeted to GPCRs have been poorly understood. Our recent study revealed that a protein complex consisting of copper metabolism MURR1 domain-containing (COMMD) 3 and 8 (COMMD3/8 complex) functions as an adaptor that recruits a specific GRK to chemoattractant receptors and plays an important role in the control of B cell migration during humoral immune responses. In this review, we summarize the current understanding of chemoattractant receptor signaling in the context of humoral immunity and discuss the potential of the COMMD3/8 complex as a therapeutic target for autoimmune diseases.

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体液免疫中的趋化受体信号传导

体液免疫反应的有效诱导取决于 B 细胞在淋巴器官内的协调迁移，而这种迁移是由 G 蛋白偶联受体（GPCR）对趋化因子为代表的趋化吸引物做出反应所控制的。配体结合后，GPCR 在受体 C 端不同位点被不同的 GPCR 激酶（GRKs）磷酸化，这决定了 β-阿司匹林介导的信号转导的功能结果，从受体失活到效应分子激活。然而，人们对单个 GRK 选择性靶向 GPCR 的分子机制还知之甚少。我们最近的研究发现，由含铜代谢 MURR1 结构域（COMMD）3 和 8 组成的蛋白复合物（COMMD3/8 复合物）可作为一种适配体，将特定的 GRK 募集到趋化吸引受体上，并在体液免疫反应过程中控制 B 细胞迁移方面发挥重要作用。在这篇综述中，我们总结了目前对体液免疫中趋化受体信号转导的理解，并讨论了 COMMD3/8 复合物作为自身免疫疾病治疗靶点的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International immunology 医学-免疫学

CiteScore

9.30

自引率

2.30%

发文量

审稿时长

6-12 weeks

期刊介绍： International Immunology is an online only (from Jan 2018) journal that publishes basic research and clinical studies from all areas of immunology and includes research conducted in laboratories throughout the world.