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

Biochim Biophys Acta Biomembr. 2021 Dec 1;1863(12):183757. doi: 10.1016/j.bbamem.2021.183757. Epub 2021 Aug 31.


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)P2 or PIP2).

Keywords: Electron microscopy; GLUT1; Glucose metabolism; Nanodiscs; PI(4,5)P(2); TXNIP (thioredoxin-interacting protein).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biological Transport / genetics
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Clathrin / chemistry
  • Endocytosis / genetics
  • Glucose / metabolism
  • Glucose Transporter Type 1 / chemistry
  • Glucose Transporter Type 1 / genetics*
  • Humans
  • Lipids / chemistry
  • Lipids / genetics*
  • Phosphatidylinositol 4,5-Diphosphate / chemistry*
  • Phosphatidylinositol 4,5-Diphosphate / genetics
  • Signal Transduction


  • Carrier Proteins
  • Clathrin
  • Glucose Transporter Type 1
  • Lipids
  • Phosphatidylinositol 4,5-Diphosphate
  • SLC2A1 protein, human
  • TXNIP protein, human
  • Glucose