Mechanisms governing GPCR anterograde transport

Article Article scientifique Revue de la littérature Mechanisms governing GPCR anterograde transport eng 2025-05-27 author Assoumou Kevin Department of Cell Physiology and Metabolism, University of Geneva, Switzerland. 870598 Département de physiologie cellulaire et métabolisme (PHYME) author Papadogkonaki Sofia Department of Cell Physiology and Metabolism, University of Geneva, Switzerland. 413002 Département de physiologie cellulaire et métabolisme (PHYME) author Muneta Arrate Itziar Department of Cell Physiology and Metabolism, University of Geneva, Switzerland. 405705 Département de physiologie cellulaire et métabolisme (PHYME) author Stoeber Miriam Carolin 0000-0002-5210-2864 Department of Cell Physiology and Metabolism, University of Geneva, Switzerland. 930635 Département de physiologie cellulaire et métabolisme (PHYME) 10.1002/1873-3468.70081 40426025 0014-5793 https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.70081 G protein-coupled receptors (GPCRs) constitute the largest family of human membrane proteins. GPCRs recognize diverse extracellular stimuli and activate intracellular signaling cascades that regulate key physiological processes such as neurotransmission and cardiovascular function. The controlled transport of nascent GPCRs from the endoplasmic reticulum (ER) via the Golgi apparatus to the cell surface critically determines the cellular responsiveness to incoming ligands. Here, we present a comprehensive overview of the cellular mechanisms and motif-driven interactions with regulatory proteins that orchestrate GPCR folding, post-translational modifications, and vesicular transport along the secretory pathway. We highlight signaling cues that can modulate the anterograde transport and specialized mechanisms that deliver biosynthetic GPCRs to dendrites and axons in neurons. Furthermore, we discuss that many disease-causing GPCR mutants exhibit aberrant intracellular retention, which can be rescued by pharmacological strategies that stabilize misfolded GPCRs. Finally, we highlight insights into the agonist-driven signaling of biosynthetic GPCRs in secretory organelles. This review covers the complex roles of anterograde transport in controlling GPCR function and emerging possibilities to target the underlying mechanisms in disease. G protein‐coupled receptor Golgi apparatus Anterograde transport Endoplasmic reticulum Neuron Pharmacological chaperone Post‐translational modification Secretory pathway Signaling Trafficking motif Dewey 612 Swiss National Science Foundation Decoding the intracellular localization and function of class A GPCRs 10002302 CH Projects 134 Département de physiologie cellulaire et métabolisme 21C false 1283 Contrôle subcellulaire des récepteurs de signalisation 1005 FEBS letters 8aca6159-1e44-4aaa-a4d7-4c147e80bb8d Article (Published version) Public FEBS_Letters_-_2025_-_Assoumou_-_Me.pdf 2153043 application/pdf 568b38b555ca2af7e218c7c64804c4df1d790802c92454a891225bb843e119e5 834374e4-ba92-472c-a19a-508ce88c205a Supplemental data Public feb270081-sup-0001-tables1.docx 33018 application/vnd.openxmlformats-officedocument.wordprocessingml.document 6c61179a3a6fa969a8178d492f04a1b3b24c2b590ce0d8369549cf1511b282c0 openAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

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Mechanisms governing GPCR anterograde transport	FEBS letters			2025	51	86

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