ArticleMolecular endocrinology (Baltimore, Md.)2013
The identification of novel proteins that interact with the GLP-1 receptor and restrain its activity.
Article in Molecular endocrinology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Major Facilitator Superfamily Domain Containing 5 Inhibition Reduces Lipoprotein(a) Uptake and Calcification in Valvular Heart Disease.Circulation · 2024Pooled it
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Signaling architecture of the glucagon-like peptide-1 receptor.The Journal of clinical investigation · 2026Review
- Multi-faceted roles of β-arrestins in G protein-coupled receptor endocytosis.Nature communications · 2025Article
- C18ORF32 modulates lipid droplet secretion via secretory autophagy and restrains hepatic steatosis in vivo.Cell communication and signaling : CCS · 2025Article
- Integrated Genetic and Protein Mechanisms Underlying Glucagon-like Peptide-1 Receptor Agonists in Treating Diabetes Mellitus and Weight Loss.Current issues in molecular biology · 2025Article
- Endogenous cell membrane interactome mapping for the GLP-1 receptor in different cell types.Nature chemical biology · 2025Article
- Spint1 disruption in mouse pancreas leads to glucose intolerance and impaired insulin production involving HEPSIN/MAFA.Nature communications · 2024Article
- The bs5 allele of the susceptibility gene Bs5 of pepper (Capsicum annuum L.) encoding a natural deletion variant of a CYSTM protein conditions resistance to bacterial spot disease caused by Xanthomonas species.TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik · 2023Article
- SYNGR4 and PLEKHB1 deregulation in motor neurons of amyotrophic lateral sclerosis models: potential contributions to pathobiology.Neural regeneration research · 2022Review
- Role of adaptin protein complexes in intracellular trafficking and their impact on diseases.Bioengineered · 2021Article
- Identification of TSPAN4 as Novel Histamine HBiomolecules · 2021Article
- Agonist-induced membrane nanodomain clustering drives GLP-1 receptor responses in pancreatic beta cells.PLoS biology · 2019Article
- Cerebrospinal Fluid Proteomics For Identification Of α2-Macroglobulin As A Potential Biomarker To Monitor Pharmacological Therapeutic Efficacy In Dopamine Dictated Disease States Of Parkinson's Disease And Schizophrenia.Neuropsychiatric disease and treatment · 2019Article
- Melatonin receptors limit dopamine reuptake by regulating dopamine transporter cell-surface exposure.Cellular and molecular life sciences : CMLS · 2018Article
- Scaffold Proteins: From Coordinating Signaling Pathways to Metabolic Regulation.Endocrinology · 2018Review
- Article
- Systematic protein-protein interaction mapping for clinically relevant human GPCRs.Molecular systems biology · 2017Article
- Osteopontin activates the diabetes-associated potassium channel TALK-1 in pancreatic β-cells.PloS one · 2017Article
- Acute appendicitis: transcript profiling of blood identifies promising biomarkers and potential underlying processes.BMC medical genomics · 2016Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Glucagon-like peptide 1 receptor (GLP-1R) controls diverse physiological functions in tissues including the pancreatic islets, brain, and heart. To understand the mechanisms that control glucagon-like peptide 1 (GLP-1) signaling better, we sought to identify proteins that interact with the GLP-1R using a membrane-based split ubiquitin yeast two-hybrid (MYTH) assay. A screen of a human fetal brain cDNA prey library with an unliganded human GLP-1R as bait in yeast revealed 38 novel interactor protein candidates. These interactions were confirmed in mammalian Chinese hamster ovarian cells by coimmunoprecipitation. Immunofluorescence was used to show subcellular colocalization of the interactors with GLP-1R. Cluster analysis revealed that the interactors were primarily associated with signal transduction, metabolism, and cell development. When coexpressed with the GLP-1R in Chinese hamster ovarian cells, 15 interactors significantly altered GLP-1-induced cAMP accumulation. Surprisingly, all 15 proteins inhibited GLP-1-activated cAMP. Given GLP-1's prominent role as an incretin, we then focused on 3 novel interactors, SLC15A4, APLP1, and AP2M1, because they are highly expressed and localized to the membrane in mouse insulinoma β-cells. Small interfering RNA-mediated knockdown of each candidate gene significantly enhanced GLP-1-induced insulin secretion. In conclusion, we have generated a novel GLP-1R-protein interactome, identifying several interactors that suppress GLP-1R signaling. We suggest that the inhibition of these interactors may serve as a novel strategy to enhance GLP-1R activity.
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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.