ArticleCell reports2017
Integration of GPCR Signaling and Sorting from Very Early Endosomes via Opposing APPL1 Mechanisms.
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 103 citations in OpenAlex.
- Inhibitory probes for spatiotemporal analysis of GαNature chemical biology · 2026Article
- Spatiotemporal modeling of GPCR signaling: The role of endosomal dynamics and receptor recycling.PLoS computational biology · 2026Article
- Short-chain fatty acids.Nature metabolism · 2026Review
- Membrane lipid poly-unsaturation selectively affects dopamine D2 receptor endocytosis.Nature communications · 2026Article
- Chemical biology approaches to resolve the subcellular GPCR signaling landscape.Nature chemical biology · 2025Review
- A calcium-sensing receptor dileucine motif directs internalization to spatially distinct endosomal signaling pathways.iScience · 2025Article
- Pharmacogenomic of LH and its receptor: are we ready for clinical practice?Reproductive biology and endocrinology : RB&E · 2025Review
- Measuring Calcium-Sensing Receptor Agonist-Driven Insertional Signaling (ADIS) and Trafficking by TIRF Microscopy.Methods in molecular biology (Clifton, N.J.) · 2025Article
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- Constitutive internalisation of EP2 differentially regulates G protein signalling.Journal of molecular endocrinology · 2024Article
- Biomimetic proteolipid vesicles for reverting GPI deficiency in paroxysmal nocturnal hemoglobinuria.iScience · 2024Article
- β-Arrestin-independent endosomal cAMP signaling by a polypeptide hormone GPCR.Nature chemical biology · 2024Article
- Highly-Sensitive In Vitro Bioassays for FSH, TSH, PTH, Kp, and OT in Addition to LH in Mouse Leydig Tumor Cell.International journal of molecular sciences · 2023Article
- Vesicle-associated membrane protein 2 is a cargo-selective v-SNARE for a subset of GPCRs.The Journal of cell biology · 2023Article
- A Rab10-ACAP1-Arf6 GTPases cascade modulates M4 muscarinic acetylcholine receptor trafficking and signaling.Cellular and molecular life sciences : CMLS · 2023Article
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- Article
- Review
- Intracellular VHHs to monitor and modulate GPCR signaling.Frontiers in endocrinology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 7 institutions in 3 countries.
Funding
Abstract
Endocytic trafficking is a critical mechanism for cells to decode complex signaling pathways, including those activated by G-protein-coupled receptors (GPCRs). Heterogeneity in the endosomal network enables GPCR activity to be spatially restricted between early endosomes (EEs) and the recently discovered endosomal compartment, the very early endosome (VEE). However, the molecular machinery driving GPCR activity from the VEE is unknown. Using luteinizing hormone receptor (LHR) as a prototype GPCR for this compartment, along with additional VEE-localized GPCRs, we identify a role for the adaptor protein APPL1 in rapid recycling and endosomal cAMP signaling without impacting the EE-localized β2-adrenergic receptor. LHR recycling is driven by receptor-mediated Gαs/cAMP signaling from the VEE and PKA-dependent phosphorylation of APPL1 at serine 410. Receptor/Gαs endosomal signaling is localized to microdomains of heterogeneous VEE populations and regulated by APPL1 phosphorylation. Our study uncovers a highly integrated inter-endosomal communication system enabling cells to tightly regulate spatially encoded signaling.
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Registered trials
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.