ArticleThe Journal of biological chemistry2014
Spatially restricted G protein-coupled receptor activity via divergent endocytic compartments.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 116 citations in OpenAlex.
- Spatiotemporal modeling of GPCR signaling: The role of endosomal dynamics and receptor recycling.PLoS computational biology · 2026Article
- Short-chain fatty acids.Nature metabolism · 2026Review
- Differential conservation analysis identifies residues defining constitutive internalization in beta-adrenergic receptors.iScience · 2026Article
- Intersection of GPCR trafficking and cAMP signaling at endomembranes.The Journal of cell biology · 2025Review
- Endogenous ligands of bovine FFAR2/GPR43 display distinct pharmacological properties.Frontiers in cell and developmental biology · 2025Article
- Myosin VI drives arrestin-independent internalization and signaling of GPCRs.Nature communications · 2024Article
- Article
- Constitutive internalisation of EP2 differentially regulates G protein signalling.Journal of molecular endocrinology · 2024Article
- Spatiotemporal regulation of the hepatocyte growth factor receptor MET activity by sorting nexins 1/2 in HCT116 colorectal cancer cells.Bioscience reports · 2024Article
- β-Arrestin-independent endosomal cAMP signaling by a polypeptide hormone GPCR.Nature chemical biology · 2024Article
- GPCR kinases differentially modulate biased signaling downstream of CXCR3 depending on their subcellular localization.Science signaling · 2024Article
- Granulosa Cells Alone, Without Theca Cells, Can Mediate LH-induced Oocyte Meiotic Resumption.Endocrinology · 2024Article
- Specific Signal Transduction of Constitutively Activating (D576G) and Inactivating (R476H) Mutants of Agonist-Stimulated Luteinizing Hormone Receptor in Eel.International journal of molecular sciences · 2023Article
- A Rab10-ACAP1-Arf6 GTPases cascade modulates M4 muscarinic acetylcholine receptor trafficking and signaling.Cellular and molecular life sciences : CMLS · 2023Article
- Expression and function of the luteinizing hormone choriogonadotropin receptor in human endometrial stromal cells.Scientific reports · 2022Article
- The organic cation transporter 2 regulates dopamine D1 receptor signaling at the Golgi apparatus.eLife · 2022Article
- Intracellular VHHs to monitor and modulate GPCR signaling.Frontiers in endocrinology · 2022Review
- Constitutively Activating Mutants of Equine LH/CGR Constitutively Induce Signal Transduction and Inactivating Mutations Impair Biological Activity and Cell-Surface Receptor Loss In Vitro.International journal of molecular sciences · 2021Article
- ERβ Regulation of Gonadotropin Responses during Folliculogenesis.International journal of molecular sciences · 2021Review
- Mechanisms of selective G protein-coupled receptor localization and trafficking.Current opinion in cell biology · 2021Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Postendocytic sorting of G protein-coupled receptors (GPCRs) is driven by their interactions between highly diverse receptor sequence motifs with their interacting proteins, such as postsynaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), zonula occludens-1 protein (zo-1) (PDZ) domain proteins. However, whether these diverse interactions provide an underlying functional specificity, in addition to driving sorting, is unknown. Here we identify GPCRs that recycle via distinct PDZ ligand/PDZ protein pairs that exploit their recycling machinery primarily for targeted endosomal localization and signaling specificity. The luteinizing hormone receptor (LHR) and β2-adrenergic receptor (B2AR), two GPCRs sorted to the regulated recycling pathway, underwent divergent trafficking to distinct endosomal compartments. Unlike B2AR, which traffics to early endosomes (EE), LHR internalizes to distinct pre-early endosomes (pre-EEs) for its recycling. Pre-EE localization required interactions of the LHR C-terminal tail with the PDZ protein GAIP-interacting protein C terminus, inhibiting its traffic to EEs. Rerouting the LHR to EEs, or EE-localized GPCRs to pre-EEs, spatially reprograms MAPK signaling. Furthermore, LHR-mediated activation of MAPK signaling requires internalization and is maintained upon loss of the EE compartment. We propose that combinatorial specificity between GPCR sorting sequences and interacting proteins dictates an unprecedented spatiotemporal control in GPCR signal activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.