Gq-Coupled Receptors in Autoimmunity.

Lu Zhang,Guixiu Shi

doi:10.1155/2016/3969023

Abstract

Heterotrimeric G proteins can be divided into Gi, Gs, Gq/11, and G12/13 subfamilies according to their α subunits. The main function of G proteins is transducing signals from G protein coupled receptors (GPCRs), a family of seven transmembrane receptors. In recent years, studies have demonstrated that GPCRs interact with Gq, a member of the Gq/11 subfamily of G proteins. This interaction facilitates the vital role of this family of proteins in immune regulation and autoimmunity, particularly for Gαq, which is considered the functional α subunit of Gq protein. Therefore, understanding the mechanisms through which Gq-coupled receptors control autoreactive lymphocytes is critical and may provide insights into the treatment of autoimmune disorders. In this review, we summarize recent advances in studies of the role of Gq-coupled receptors in autoimmunity, with a focus on their pathologic role and downstream signaling.

Highlights

Many receptors for hormones, neurotransmitters, neuropeptides, chemokines, and autocrine and paracrine signaling molecules interact with heterotrimeric G proteins to exert their actions on target cells [1]; these receptors are considered G protein coupled receptors (GPCRs) [2]
Heterotrimeric G proteins consist of an α-subunit, which binds to and hydrolyzes guanosine-5󸀠-triphosphate (GTP), and β- and γ-subunits, which form an indissociable complex [4]
Gq-coupled GPCRs on different lymphocytes can transduce a series of extracellular signals into the nucleus to regulate immune function

Summary

Introduction

Many receptors for hormones, neurotransmitters, neuropeptides, chemokines, and autocrine and paracrine signaling molecules interact with heterotrimeric G proteins to exert their actions on target cells [1]; these receptors are considered G protein coupled receptors (GPCRs) [2]. Gαq-GTP and the Gβγ dimer transmit receptor-generated signals to downstream effector molecules and protein binding partners until the intrinsic GTPase activity of Gα hydrolyzes GTP to GDP and the inactive subunits reassociate [6]; this is called the “active and inactive” cycle. The Gq/11 subfamily, including Gq, G11, G14, and G15/16, shares structural similarity, and activation of the α subunit within each protein complex can activate PLC-β [4,5,6,7] All of these four subunits regulate both overlapping and distinct signaling pathways, thereby stimulating inositol lipid (i.e., calcium/protein kinase C (PKC)) signaling through PLC-β isoforms [1, 4,5,6,7,8,9]. Abnormal regulation of these receptors may be associated with the pathogenesis of autoimmunity and a variety of autoimmune diseases induced by autoreactive lymphocytes, leading to morbidity and mortality in individuals with autoimmune disorders [19,20,21,22,23,24]

The Diversity of Gq-Coupled Receptors in Autoimmunity

How Do Gq-Coupled Receptors Play a Role in Autoimmunity?

Induction of T-Cell Proliferation by GqPCR

Perspectives