ArticleThe Journal of biological chemistry2013
Constitutive internalization of the leucine-rich G protein-coupled receptor-5 (LGR5) to the trans-Golgi network.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- LGR5: from stem cell marker to therapeutic target.Trends in cancer · 2026Review
- Cetuximab increases LGR5 expression and augments LGR5-targeting antibody-drug conjugate efficacy in patient-derived colorectal cancer models.Cell reports. Medicine · 2025Article
- Cetuximab increases LGR5 expression and augments LGR5-targeting antibody-drug conjugate efficacy in patient-derived colorectal cancer models.bioRxiv : the preprint server for biology · 2025Article
- Functional and Biological Characterization of the LGR5Δ5 Splice Variant in HEK293T Cells.International journal of molecular sciences · 2024Article
- Novel immunotherapeutics against LGR5 to target multiple cancer types.EMBO molecular medicine · 2024Article
- Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity.eLife · 2024Article
- LGR4 and LGR5 form distinct homodimers that only LGR4 complexes with RNF43/ZNRF3 to provide high affinity binding of R-spondin ligands.Scientific reports · 2023Article
- Functional patient-derived organoid screenings identify MCLA-158 as a therapeutic EGFR × LGR5 bispecific antibody with efficacy in epithelial tumors.Nature cancer · 2022Article
- Receptor control by membrane-tethered ubiquitin ligases in development and tissue homeostasis.Current topics in developmental biology · 2022Article
- Unlike LGR4, LGR5 potentiates Wnt-β-catenin signaling without sequestering E3 ligases.Science signaling · 2020Article
- The kinase PERK represses translation of the G-protein-coupled receptor LGR5 and receptor tyrosine kinase ERBB3 during ER stress in cancer cells.The Journal of biological chemistry · 2020Article
- Article
- Differential activities and mechanisms of the four R-spondins in potentiating Wnt/β-catenin signaling.The Journal of biological chemistry · 2018Article
- Leucine-rich G Protein-coupled Receptor-5 Is Significantly Increased in the Aqueous Humor of Human Eye with Proliferative Diabetic Retinopathy.Experimental neurobiology · 2018Article
- Biased signalling: from simple switches to allosteric microprocessors.Nature reviews. Drug discovery · 2018Review
- Role of Rab GTPases in the export trafficking of G protein-coupled receptors.Small GTPases · 2018Review
- LGR5 receptor promotes cell-cell adhesion in stem cells and colon cancer cells via the IQGAP1-Rac1 pathway.The Journal of biological chemistry · 2017Article
- Inhibiting clathrin-mediated endocytosis of the leucine-rich G protein-coupled receptor-5 diminishes cell fitness.The Journal of biological chemistry · 2017Article
- Probing the Allosteric Role of the α5 Subunit of α3β4α5 Nicotinic Acetylcholine Receptors by Functionally Selective Modulators and Ligands.ACS chemical biology · 2017Article
- Rimonabant Kills Colon Cancer Stem Cells without Inducing Toxicity in Normal Colon Organoids.Frontiers in pharmacology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
LGR5 is a Wnt pathway associated G protein-coupled receptor (GPCR) that serves as a molecular determinant of stem cells in numerous tissues including the intestine, stomach, hair follicle, eye, and mammary gland. Despite its importance as a marker for this critical niche, little is known about LGR5 signaling nor the biochemical mechanisms and receptor determinants that regulate LGR5 membrane expression and intracellular trafficking. Most importantly, in cells LGR5 is predominantly intracellular, yet the mechanisms underlying this behavior have not been determined. In this work we elucidate a precise trafficking program for LGR5 and identify the motif at its C terminus that is responsible for the observed constitutive internalization. We show that this process is dependent upon dynamin GTPase activity and find that wild-type full-length LGR5 rapidly internalizes into EEA1- and Rab5-positive endosomes. However, LGR5 fails to rapidly recycle to the plasmid membrane through Rab4-positive vesicles, as is common for other GPCRs. Rather, internalized LGR5 transits through Rab7- and Rab9-positive vesicles, co-localizes in vesicles with Vps26, a retromer complex component that regulates retrograde trafficking to the trans-Golgi network (TGN) and reaches a steady-state distribution in the TGN within 2 h. Using mutagenesis, particularly of putative phosphorylation sites, we show that the amino acid pair, serine 861 and 864, is the principal C-tail determinant that mediates LGR5 constitutive internalization. The constitutive internalization of LGR5 to the TGN suggests the existence of novel biochemical roles for its Wnt pathway related, but ill defined signaling program.
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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.