BAG6 contributes to glucose uptake by supporting the cell surface translocation of the glucose transporter GLUT4

Biol Open. 2020 Jan 24;9(1):bio047324. doi: 10.1242/bio.047324.


Defective translocation of glucose transporter 4 (GLUT4) to the cell surface is a key feature of insulin resistance in type 2 diabetes. Therefore, elucidating the mechanism of GLUT4 translocation is of primary importance. The mammalian Bag6/Bat3 gene has been suggested to be linked with potential obesity- and diabetes-associated loci, while its function in the control of glucose incorporation into the cytoplasm has not been investigated. In this study, we established a series of cell lines that stably expressed GLUT4 with three tandem repeats of the antigenic peptide inserted into its 1st extracellular loop. With these cell lines, we found that the depletion of endogenous BAG6 downregulated the cell surface expression of GLUT4, concomitant with the reduced incorporation of a glucose analog into the cells. Defective intracellular translocation of GLUT4 in BAG6-depleted cells is similar to the case observed for the depletion of Rab8a, an essential regulator of insulin-stimulated GLUT4 translocation. In addition, we observed that the assembly of syntaxin 6 into the endoplasmic reticulum membrane was slightly disturbed under BAG6 depletion. Given that Rab8a and syntaxin 6 are critical for GLUT4 translocation, we suggest that BAG6 may play multiple roles in the trafficking of glucose transporters to the cell surface.This article has an associated First Person interview with the first author of the paper.

Keywords: BAT3; Diabetes; Membrane trafficking; Obesity; Rab8a; Scythe.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cell Line
  • Cell Membrane / metabolism*
  • Cricetinae
  • Cricetulus
  • Glucose / metabolism*
  • Glucose Transport Proteins, Facilitative / genetics
  • Glucose Transport Proteins, Facilitative / metabolism*
  • Glucose Transporter Type 4 / chemistry
  • Glucose Transporter Type 4 / genetics
  • Glucose Transporter Type 4 / metabolism
  • Insulin / metabolism
  • Mice
  • Models, Molecular
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Transport


  • Bag6 protein, mouse
  • Glucose Transport Proteins, Facilitative
  • Glucose Transporter Type 4
  • Insulin
  • Molecular Chaperones
  • Nuclear Proteins
  • Glucose