ArticlePLoS genetics2013
Widespread dysregulation of peptide hormone release in mice lacking adaptor protein AP-3.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- Identification of the functional domain of the dense core vesicle biogenesis factor HID-1.PloS one · 2023Article
- SNX5 targets a monoamine transporter to the TGN for assembly into dense core vesicles by AP-3.The Journal of cell biology · 2022Article
- Pancreatic β-Cell-Specific Deletion of VPS41 Causes Diabetes Due to Defects in Insulin Secretion.Diabetes · 2021Article
- Differential sorting behavior for soluble and transmembrane cargoes at theMolecular biology of the cell · 2020Article
- Coatopathies: Genetic Disorders of Protein Coats.Annual review of cell and developmental biology · 2019Review
- Lysosome-related organelles as functional adaptations of the endolysosomal system.Current opinion in cell biology · 2019Review
- The road to lysosome-related organelles: Insights from Hermansky-Pudlak syndrome and other rare diseases.Traffic (Copenhagen, Denmark) · 2019Review
- Synaptic Vesicle Recycling Pathway Determines Neurotransmitter Content and Release Properties.Neuron · 2019Article
- Coupling of microtubule motors with AP-3 generated organelles in axons by NEEP21 family member calcyon.Molecular biology of the cell · 2018Article
- Neuronal functions of adaptor complexes involved in protein sorting.Current opinion in neurobiology · 2018Review
- Control of insulin granule formation and function by the ABC transporters ABCG1 and ABCA1 and by oxysterol binding protein OSBP.Molecular biology of the cell · 2018Article
- Remodeling the Specificity of an Endosomal CORVET Tether Underlies Formation of Regulated Secretory Vesicles in the Ciliate Tetrahymena thermophila.Current biology : CB · 2018Article
- HID-1 controls formation of large dense core vesicles by influencing cargo sorting andMolecular biology of the cell · 2017Article
- Osteoclast stimulation factor 1 (Ostf1) KNOCKOUT increases trabecular bone mass in mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2017Article
- BAIAP3, a C2 domain-containing Munc13 protein, controls the fate of dense-core vesicles in neuroendocrine cells.The Journal of cell biology · 2017Article
- α-Synuclein promotes dilation of the exocytotic fusion pore.Nature neuroscience · 2017Article
- Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway.Cell reports · 2016Article
- The EARP Complex and Its Interactor EIPR-1 Are Required for Cargo Sorting to Dense-Core Vesicles.PLoS genetics · 2016Article
- SORCS1 is necessary for normal insulin secretory granule biogenesis in metabolically stressed β cells.The Journal of clinical investigation · 2014Article
- Two dipolar α-helices within hormone-encoding regions of proglucagon are sorting signals to the regulated secretory pathway.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The regulated secretion of peptide hormones, neural peptides and many growth factors depends on their sorting into large dense core vesicles (LDCVs) capable of regulated exocytosis. LDCVs form at the trans-Golgi network, but the mechanisms that sort proteins to this regulated secretory pathway and the cytosolic machinery that produces LDCVs remain poorly understood. Recently, we used an RNAi screen to identify a role for heterotetrameric adaptor protein AP-3 in regulated secretion and in particular, LDCV formation. Indeed, mocha mice lacking AP-3 have a severe neurological and behavioral phenotype, but this has been attributed to a role for AP-3 in the endolysosomal rather than biosynthetic pathway. We therefore used mocha mice to determine whether loss of AP-3 also dysregulates peptide release in vivo. We find that adrenal chromaffin cells from mocha animals show increased constitutive exocytosis of both soluble cargo and LDCV membrane proteins, reducing the response to stimulation. We also observe increased basal release of both insulin and glucagon from pancreatic islet cells of mocha mice, suggesting a global disturbance in the release of peptide hormones. AP-3 exists as both ubiquitous and neuronal isoforms, but the analysis of mice lacking each of these isoforms individually and together shows that loss of both is required to reproduce the effect of the mocha mutation on the regulated pathway. In addition, we show that loss of the related adaptor protein AP-1 has a similar effect on regulated secretion but exacerbates the effect of AP-3 RNAi, suggesting distinct roles for the two adaptors in the regulated secretory pathway.
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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.