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G Protein-Coupled Receptors in Cell Signaling Transductions—2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 20 May 2025 | Viewed by 1051

Special Issue Editors


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Guest Editor
1. Department of Pharmacology, Experimental Therapy and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomic, 72074 Tübingen, Germany
2. Interfaculty Center for Pharmacogenomics and Drug Research, Eberhard Karls University Tübingen and University Clinic, 72076 Tübingen, Germany
Interests: G proteins; non-canonical signaling; cardiovascular disease; immune responses
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Guest Editor
Rudolf-Schönheimer-Institute for Biochemistry, University Leipzig, 04103 Leipzig, Germany
Interests: adipocytes; adhesion G protein-coupled receptors; GPCR; adhesion; mechano-activation; signal transduction; de-orphanisation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This is a continued issue of our successful Special Issue “G Protein-Coupled Receptors in Cell Signaling Transduction”.

G protein-coupled receptors (GPCRs) and their downstream signaling pathways are critical targets for current pharmacotherapy. More than one-third of the drugs in use today act on GPCRs either as agonists, inverse agonists, or antagonists; however, their therapeutic potential is not exhausted, especially since recent findings point to new pharmacotherapeutically relevant regulatory mechanisms. In particular, hitherto largely unknown non-classical or, as they are also termed, non-canonical regulatory mechanisms of GPCR signaling have been identified that can either modulate canonical signaling by G proteins or trigger unrelated signaling events. These pathways are governed by receptor classes other than GPCRs, and various non-receptor regulators, including activators of G protein signaling (AGS) proteins or phosphate transferring nucleoside diphosphate kinases (NDPKs). GPCR adapters, such as arrestins and regulators of G protein signaling (RGS), can exert additional functions distinct from the inactivation of G protein signaling. Original research articles, reviews, and communications on the (patho)physiological relevance of canonical as well as non-canonical GPCR signaling in biological processes, such as tumor progression, autophagy, and cell movement, which are crucial for major human diseases, including cancer, metabolic disorders, cardiovascular diseases, immune responses, and (neuro-)sensory defects, will be particularly appreciated.

Prof. Dr. Sandra Beer-Hammer
Prof. Dr. Ines Liebscher
Guest Editors

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Keywords

  • GPCRs
  • G-Proteins
  • canonical/non-canonical signaling
  • AGS proteins
  • RGS proteins
  • β-arrestin
  • NDPKs
  • pharmacological intervention
  • biased ligands

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Published Papers (1 paper)

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Research

14 pages, 1521 KiB  
Article
Unveiling the Role of Two Rhodopsin-like GPCR Genes in Insecticide-Resistant House Flies, Musca domestica
by Juanjuan Xin, Dylan Brown, Yifan Wang, Xin Wang, Ming Li, Ting Li and Nannan Liu
Int. J. Mol. Sci. 2024, 25(19), 10618; https://doi.org/10.3390/ijms251910618 - 2 Oct 2024
Viewed by 595
Abstract
Insecticide resistance in insects, driven by the overexpression of P450 enzymes, presents a significant challenge due to the enhanced metabolic detoxification of insecticides. Although the transcriptional regulation of P450 genes is not yet fully understood, G-protein-coupled receptor (GPCR) genes have emerged as key [...] Read more.
Insecticide resistance in insects, driven by the overexpression of P450 enzymes, presents a significant challenge due to the enhanced metabolic detoxification of insecticides. Although the transcriptional regulation of P450 genes is not yet fully understood, G-protein-coupled receptor (GPCR) genes have emerged as key regulators in this process. This study is the first to associate GPCR genes with insecticide resistance in Musca domestica. We identified two key rhodopsin-like GPCR genes, ALHF_02706.g1581 and ALHF_04422.g2918, which were significantly overexpressed in the resistant ALHF strain compared to sensitive strains. Notably, both ALHF_02706.g1581 and ALHF_04422.g2918 were mapped to autosome 2, where critical but unidentified regulatory factors controlling resistance and P450 gene regulation are located. This supports our hypothesis that GPCRs function as trans-regulatory factors for P450-mediated resistance. Functional analysis using transgenic Drosophila demonstrated that overexpression of these rhodopsin-like GPCR genes increased permethrin resistance by approximately two-fold. Specifically, ALHF_02706.g1581 overexpression significantly upregulated the Drosophila resistance-related P450 genes CYP12D1, CYP6A2, and CYP6A8, while ALHF_04422.g2918 increased CYP6G1 and CYP6A2 expression, thereby enhancing insecticide detoxification in rhodopsin-like GPCR transgenic Drosophila lines. These findings suggest that these rhodopsin-like GPCR genes on autosome 2 may act as trans-regulatory factors for P450-mediated resistance, underscoring their critical role in insecticide detoxification and resistance development in M. domestica. Full article
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