TXNIP interaction with GLUT1 depends on PI(4,5)P2.

GLUT1 is a major glucose facilitator expressed ubiquitously among tissues. Upregulation of its expression plays an important role in the development of many types of cancer and metabolic diseases. Thioredoxin-interacting protein (TXNIP) is an α-arrestin that acts as an adaptor for GLUT1 in clathrin-mediated endocytosis. It regulates cellular glucose uptake in response to both intracellular and extracellular signals via its control on GLUT1‐4. In order to understand the interaction between GLUT1 and TXNIP, we generated GLUT1 lipid nanodiscs and carried out isothermal titration calorimetry and single-particle electron microscopy experiments. We found that GLUT1 lipid nanodiscs and TXNIP interact in a 1:1 ratio and that this interaction requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 or PIP 2). [Display omitted] • GLUT1 incorporates into lipid nanodisc using MSP1E3 protein. • Electron microscopy shows TXNIP interaction with GLUT1 in a 1:1 ratio. • TXNIP-GLUT1 interaction depends on TXNIP interaction with the phospholipid PIP 2. • TXNIP-GLUT1 interaction is specific; TXNIP does not interact with GLUT5. [ABSTRACT FROM AUTHOR]