New Insights in G protein-coupled receptors (GPCRs) and Small GTPase-Associated Signaling Pathways – In Memory of Professor Audrey Claing

As the largest family of transmembrane receptors, G protein-coupled receptors (GPCRs) regulate a vast array of physiological processes and are involved in many pathological conditions. Reflecting their central biological importance, more than 35% of marketed drugs target GPCRs. Yet, despite their therapeutic relevance, many aspects of GPCR signaling and intracellular signal integration remain incompletely understood.Beyond heterotrimeric G proteins, another major class of signaling regulators operating downstream of GPCRs are the small G proteins of the Ras superfamily, including RhoA, Rac1, Cdc42, Ras, and ADP-ribosylation factors (ARFs). Acting as molecular switches through their GTP/GDP cycling, these proteins regulate essential cellular processes such as cytoskeletal remodeling as well as cell proliferation, survival, trafficking and migration. Positioned downstream of both GPCRs and receptor tyrosine kinases (RTKs), small GTPases integrate signaling networks that are frequently dysregulated in cancer and vascular diseases, thereby promoting tumor growth, invasion, immune evasion, angiogenesis, and vascular smooth muscle cell dysfunction.The collective work of Prof. Audrey Claing has significantly advanced our understanding of these signaling processes. Her research uncovered fundamental roles for ARF family GTPases as critical regulators of membrane trafficking, actin cytoskeleton remodeling, lipid dynamics, and vesicle formation downstream of GPCR activation. Through pioneering studies on ARF1 and ARF6 signaling pathways, her laboratory elucidated molecular mechanisms controlling receptor endocytosis, cell migration, and signal transduction, while also demonstrating how dysregulated localization and activation of ARF proteins contribute to breast cancer progression, vascular remodeling, and atherosclerosis. As master regulators of intracellular signaling and trafficking, ARF proteins have emerged as promising therapeutic targets with broad implications for pharmacological intervention across cancer, cardiovascular disease, and inflammatory disorders. A central focus of her work was to advance our understanding of the molecular mechanisms governing ARF activation and the signaling pathways coordinated by small GTPases.In honor of Prof. Audrey Claing, who’s scientific legacy was interrupted to soon by her passing, this Research Topic will highlight recent advances in our understanding of GPCR- and small GTPase-associated signaling pathways, and how their regulation contributes to physiological responses and disease progression, further expanding on their translational and therapeutic potential.Original research articles, reviews, perspectives, and commentaries related, but not limited, to the following topics are welcome:• Molecular mechanisms regulating small G proteins and/or GPCR • GPCR- and small G protein-dependent regulation of trafficking, cytoskeletal remodeling, and cell migration • Pharmacological modulation of GPCRs and small GTPases as therapeutic targets• GPCR- and small GTPase-associated signaling in cancer, metastasis, vascular biology, and other pathophysiological processesThe Topic Editor Dr. Michel Bouvier declares the following conflicts of interest: President of the Scientific Advisory Board of Kainova Therapeutics; Member of the Scientific Advisory Board of Deep Apple; Member of the Scientific Advisory Board of Interax Biotech; Co-Founder of Drave Therapeutics; licensing agreement with Kainova Therapeutics; funding from Kainova Therapeutics for a collaborative project; research contract agreement with Innospera Pharma. Topic editors: Jean-Philippe Gratton, Michel Bouvier, Stéphane Alain Laporte Source: https://www.frontiersin.org/research-topics/81557/new-insights-in-g-protein-coupled-receptors-gpcrs-and-small-gtpase-associated-signaling-pathways---in-memory-of-professor-audrey-claing