ArticleMolecular biology of the cell2010
Insulin-regulated aminopeptidase is a key regulator of GLUT4 trafficking by controlling the sorting of GLUT4 from endosomes to specialized insulin-regulated vesicles.
Article in Molecular biology of the cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 71 citations in OpenAlex.
- Glucose Transporters: Structure, Trafficking, Physiology, and Disease Relevance.Current issues in molecular biology · 2026Review
- Article
- Lipid-induced S-palmitoylation of Insulin-Responsive Aminopeptidase (IRAP) drives the onset of insulin resistance in the heart.Cellular and molecular life sciences : CMLS · 2026Article
- Proteomic Analysis of Regulated Dendritic Cell Endosomes Reveals Dynamic Adaptation to Antigen Uptake and Cross-Presentation.European journal of immunology · 2026Article
- GLUT4 Trafficking and Storage Vesicles: Molecular Architecture, Regulatory Networks, and Their Disruption in Insulin Resistance.International journal of molecular sciences · 2025Review
- Sexual and Metabolic Differences in Hippocampal Evolution: Alzheimer's Disease Implications.Life (Basel, Switzerland) · 2024Review
- Stabilization of the open conformation οf insulin-regulated aminopeptidase by a novel substrate-selective small-molecule inhibitor.Protein science : a publication of the Protein Society · 2024Article
- Potential Effects of Hyperglycemia on SARS-CoV-2 Entry Mechanisms in Pancreatic Beta Cells.Viruses · 2024Review
- Inhibition of insulin-regulated aminopeptidase confers neuroprotection in a conscious model of ischemic stroke.Scientific reports · 2023Article
- Insulin-regulated aminopeptidase is required for water excretion in response to acute hypotonic stress.American journal of physiology. Renal physiology · 2023Article
- A high-content endogenous GLUT4 trafficking assay reveals new aspects of adipocyte biology.Life science alliance · 2023Article
- Review
- GLUT4 On the move.The Biochemical journal · 2022Article
- Beta-Sitosterol Facilitates GLUT4 Vesicle Fusion on the Plasma Membrane via the Activation of Rab/IRAP/Munc 18 Signaling Pathways in Diabetic Gastrocnemius Muscle of Adult Male Rats.Bioinorganic chemistry and applications · 2022Article
- CHC22 clathrin mediates traffic from early secretory compartments for human GLUT4 pathway biogenesis.The Journal of cell biology · 2020Article
- GluT4: A central player in hippocampal memory and brain insulin resistance.Experimental neurology · 2020Review
- The Role of Insulin Regulated Aminopeptidase in Endocytic Trafficking and Receptor Signaling in Immune Cells.Frontiers in molecular biosciences · 2020Review
- Is There an Interplay Between the Functional Domains of IRAP?Frontiers in cell and developmental biology · 2020Review
- GLUT4 Storage Vesicles: Specialized Organelles for Regulated Trafficking.The Yale journal of biology and medicine · 2019Review
- Insulin-responsive amino peptidase follows the Glut4 pathway but is dispensable for the formation and translocation of insulin-responsive vesicles.Molecular biology of the cell · 2019Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Insulin stimulates glucose uptake by regulating translocation of the GLUT4 glucose transporter from intracellular compartments to the plasma membrane. In the absence of insulin GLUT4 is actively sequestered away from the general endosomes into GLUT4-specialized compartments, thereby controlling the amount of GLUT4 at the plasma membrane. Here, we investigated the role of the aminopeptidase IRAP in GLUT4 trafficking. In unstimulated IRAP knockdown adipocytes, plasma membrane GLUT4 levels are elevated because of increased exocytosis, demonstrating an essential role of IRAP in GLUT4 retention. Current evidence supports the model that AS160 RabGAP, which is required for basal GLUT4 retention, is recruited to GLUT4 compartments via an interaction with IRAP. However, here we show that AS160 recruitment to GLUT4 compartments and AS160 regulation of GLUT4 trafficking were unaffected by IRAP knockdown. These results demonstrate that AS160 is recruited to membranes by an IRAP-independent mechanism. Consistent with a role independent of AS160, we showed that IRAP functions in GLUT4 sorting from endosomes to GLUT4-specialized compartments. This is revealed by the relocalization of GLUT4 to endosomes in IRAP knockdown cells. Although IRAP knockdown has profound effects on GLUT4 traffic, GLUT4 knockdown does not affect IRAP trafficking, demonstrating that IRAP traffics independent of GLUT4. In sum, we show that IRAP is both cargo and a key regulator of the insulin-regulated 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.