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G protein-coupled receptors (GPCRs) play an essential role in the regulation of many physiological processes, and they represent a major target for already validated as well as newly emerging drugs in various therapeutic areas. The most recent advances in the field have uncovered the pleiotropy and richness ...

G protein-coupled receptors (GPCRs) play an essential role in the regulation of many physiological processes, and they represent a major target for already validated as well as newly emerging drugs in various therapeutic areas. The most recent advances in the field have uncovered the pleiotropy and richness in GPCR signal transduction. A given GPCR might preferentially regulate a particular signaling pathway with specific consequences on cellular function. Furthermore, GPCRs can modulate intracellular signaling pathways with different spatio-temporal dynamics and functional consequences. To do so, GPCRs are able to engage different signal transducers and signaling/regulatory partners in response to different ligands and in different cellular contexts. Some of these GPCR signaling molecules integrate information from different sources and constitute signaling hubs recently identified as highly relevant in certain physio- and patho- physiological contexts. Any alterations in the expression level, subcellular location, or capability of coupling of GPCRs and their downstream signaling partners might lead to disease. Much of our knowledge on the diversity of GPCR signal transduction comes from studies on heterologous expression systems. Therefore, it becomes mandatory to validate these findings in cell-based and animal disease models.

The elucidation of the diversity of GPCR signal transduction in health and disease opens new possibilities in drug target design and it paces the way to improved therapies. The aim of this Research Topic is to present the state of the art in GPCR signal transduction in health and disease through the description of recent efforts at elucidating GPCR signaling pathways and their regulation, as well as through examples of their relevance in particular physio- and pathological contexts.

The Editors welcome DIFFERENT SUBMISSION TYPES (reviews, research articles, methods, perspectives/opinions, etc.) and invite contributions particularly covering the following areas:

- complexity of GPCR signal transduction: description of molecular interactions within GPCR signaling pathways and their regulation and dynamics that give rise to signal specificity

- elucidation of GPCR signaling molecules, pathways and signaling hubs relevant in different physio- and pathological contexts

- functional consequences of genetic variations, expression levels, partner availability, … in GPCRs or in their transduction/signaling partners

- investigation of GPCR signal transduction in relevant cell-based and animal disease models and translation of knowledge from heterologous expression systems

- unconventional modulation of the signal transduction of established or emerging GPCR drug targets by strategies beyond small-molecule GPCR ligands (nanobodies, pathway specific disruptors/inhibitors, genome editing, …)

This collection will be compiled in cooperation with ERNEST COST Action.

Keywords: GPCR, signal transduction, physiology, pathophysiology, signaling, G protein-coupled receptors, cellular, animal based models, drug target design


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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