ArticleThe Journal of biological chemistry2015
A Novel GLP1 Receptor Interacting Protein ATP6ap2 Regulates Insulin Secretion in Pancreatic Beta Cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Polyadenylation of insulin mRNA by Tent5a regulates pancreatic beta cells.Nature communications · 2026Article
- Secretory stimuli distinctly regulate insulin secretory granule maturation through structural remodeling.Structure (London, England : 1993) · 2025Article
- Endogenous cell membrane interactome mapping for the GLP-1 receptor in different cell types.Nature chemical biology · 2025Article
- ATP6AP2 is robustly expressed in pancreatic β cells and neuroendocrine tumors, and plays a role in maintaining cellular viability.Scientific reports · 2023Article
- SYNGR4 and PLEKHB1 deregulation in motor neurons of amyotrophic lateral sclerosis models: potential contributions to pathobiology.Neural regeneration research · 2022Review
- Inside the Insulin Secretory Granule.Metabolites · 2021Review
- Identification of TSPAN4 as Novel Histamine HBiomolecules · 2021Article
- The HAmerican journal of physiology. Cell physiology · 2021Review
- The Pancreatic β-Cell: The Perfect Redox System.Antioxidants (Basel, Switzerland) · 2021Review
- V-ATPase blockade reduces renal gluconeogenesis and improves insulin secretion in type 2 diabetic rats.Hypertension research : official journal of the Japanese Society of Hypertension · 2020Article
- microRNA-665 silencing improves cardiac function in rats with heart failure through activation of the cAMP signaling pathway.Journal of cellular physiology · 2019Article
- The (pro)renin receptor: an emerging player in hypertension and metabolic syndrome.Kidney international · 2019Review
- The discovery of novel predictive biomarkers and early-stage pathophysiology for the transition from gestational diabetes to type 2 diabetes.Diabetologia · 2019Article
- Cellular signaling pathways regulating β-cell proliferation as a promising therapeutic target in the treatment of diabetes.Experimental and therapeutic medicine · 2018Review
- V-ATPases and osteoclasts: ambiguous future of V-ATPases inhibitors in osteoporosis.Theranostics · 2018Review
- Atp6ap2 ablation in adult mice impairs viability through multiple organ deficiencies.Scientific reports · 2017Article
- Type 2 Diabetes in the Elderly: Challenges in a Unique Patient Population.Journal of geriatric medicine and gerontology · 2016Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
GLP1 activates its receptor, GLP1R, to enhance insulin secretion. The activation and transduction of GLP1R requires complex interactions with a host of accessory proteins, most of which remain largely unknown. In this study, we used membrane-based split ubiquitin yeast two-hybrid assays to identify novel GLP1R interactors in both mouse and human islets. Among these, ATP6ap2 (ATPase H(+)-transporting lysosomal accessory protein 2) was identified in both mouse and human islet screens. ATP6ap2 was shown to be abundant in islets including both alpha and beta cells. When GLP1R and ATP6ap2 were co-expressed in beta cells, GLP1R was shown to directly interact with ATP6ap2, as assessed by co-immunoprecipitation. In INS-1 cells, overexpression of ATP6ap2 did not affect insulin secretion; however, siRNA knockdown decreased both glucose-stimulated and GLP1-induced insulin secretion. Decreases in GLP1-induced insulin secretion were accompanied by attenuated GLP1 stimulated cAMP accumulation. Because ATP6ap2 is a subunit required for V-ATPase assembly of insulin granules, it has been reported to be involved in granule acidification. In accordance with this, we observed impaired insulin granule acidification upon ATP6ap2 knockdown but paradoxically increased proinsulin secretion. Importantly, as a GLP1R interactor, ATP6ap2 was required for GLP1-induced Ca(2+) influx, in part explaining decreased insulin secretion in ATP6ap2 knockdown cells. Taken together, our findings identify a group of proteins that interact with the GLP1R. We further show that one interactor, ATP6ap2, plays a novel dual role in beta cells, modulating both GLP1R signaling and insulin processing to affect insulin secretion.
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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.