Skip to main content
Log in

Control of glucose transport by GLUT1: Regulated secretion in an unexpected environment

  • Intracellular Traffic
  • Published:
Bioscience Reports

Abstract

Studies designed to elucidate the mechanism of regulation of the GLUT1 isoform of the glucose transporter in response to a variety of cellular stresses are reviewed. Using ts mutants of vesicular stomatitis virus, it was shown that the viral L gene was responsible for the stimulation of glucose transport in infected cells. Immunofluorescence of GLUT1 demonstrated that the increase in glucose transport was the consequence of a translocation of the transporter from a reservoir in cytoplasmic vesicles to the plasma membrane. When cells were cycled between deficient and standard medium, the change in glucose transport rates was paralleled by a cycling of the transporter between the plasma membrane and the cytoplasmic vesicles. The redistribution of GLUT1 was not a consequence of a general redistribution of recycling plasma membrane proteins. Instead, the findings focus attention on the regulated exocytosis of specific membrane constituents in cells that, until recently, were not thought to exhibit this capacity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Al-Awqati, Q. (1989) Regulation of membrane transport by endocytic removal and exocytic insertion of transporters.Methods Enzymol. 172:49–59.

    Google Scholar 

  • Bell, G. I., Burant, C. F., Takeda, J. and Gould, G. W. (1993) Structure and function of mammalian facultative sugar transporters.J. Biol. Chem. 268:19161–19164.

    Google Scholar 

  • Bradbury, N. A. and Bridges, R. J. (1994) Role of membrane trafficking in plasma membrane solute transport.Am. J. Physiol. 267 (Cell Physiol. 36):C1–C24.

    Google Scholar 

  • Burgess, T. L. and Kelly, R. B. (1987) Constitutive and regulated secretion of proteins.Annu. Rev. Cell Biol. 3:243–293.

    Google Scholar 

  • Cain, C. C., Trimble, W. S. and Lienhard, G. E. (1992) Members of the VAMP family of synaptic vesicle proteins are components of the glucose transporter-containing vesicles from rat adipocytes.J. Biol. Chem. 267:11681–11684.

    Google Scholar 

  • Clark, A. E., Holman, G. D. and Kozka, I. J. (1991) Determination of the rates of appearance and loss of glucose transporters at the cell surface of rat adipose cells.Biochem. J. 278:235–241.

    Google Scholar 

  • Czech, M. P. and Buxton, J. M. (1993) Insulin action on the internalization of the GLUT4 glucose transporter in isolated rat adipocytes.J. Biol. Chem. 268:9187–9190.

    Google Scholar 

  • Davoust, J., Gruenberg, J. and Howell, K. E. (1987) Two threshold values of low pH block endocytosis at different stages.EMBO J. 6:3610–3619.

    Google Scholar 

  • Feany, M. B., Yee, A. G., Delvy, M. L. and Buckley, K. M. (1993) The synaptic vesicle proteins SV2, synaptotagmin and synaptophysin are sorted to separate cellular compartments in CHO fibroblasts.J. Cell Biol. 123:575–584.

    Google Scholar 

  • Ferro-Novick, S. and Novick, P. (1993) The role of GTP-binding proteins in transport along the exocytic pathway.Annu. Rev. Cell Biol. 9:575–599.

    Google Scholar 

  • Gould, G. W. and Bell, G. I. (1990) Facilitative glucose transporters: an expanding family.Trends Biochem. Sci. 15:18–23.

    Google Scholar 

  • Gray, M. A., Micklem, K. J., Brown, F. and Pasternak, C. A. (1983) Effects of vesicular stomatitis virus and Semliki forest virus on uptake of nutrients and intracellular cation concentration.J. Gen Virol. 64:1449–1456.

    Google Scholar 

  • Griffiths, G. and Simons, K. (1986) The trans Golgi network: sorting at the exit site of the Golgi complex.Science (Wash. DC) 234:438–443.

    Google Scholar 

  • Haney, P. M., Slot, J. W., Piper, R. C., James, D. W. and Mueckler, M. (1991) Intracellular targeting of the insulin-regulatable glucose transporter (GLUT4) is isoform specific and independent of cell type.J. Cell Biol. 114:689–699.

    Google Scholar 

  • Herman, G. A., Bonzelius, F., Cieutat, A.-M. and Kelly, R. B. (1994) A distinct class of intracellular storage vesicles, identified by expression of the glucose transporter GLUT4.Proc. Natl. Acad. Sci. USA 91:12750–12754.

    Google Scholar 

  • Holman, G. D., Lo Leggio, L. and Cushman, S. W. (1994) Insulin-stimulated GLUT4 glucose transporter recycling. A problem in membrane protein subcellular trafficking through multiple pools.J. Biol. Chem. 269:17516–17524.

    Google Scholar 

  • Hudson, A. W., Ruiz, M-L. and Birnbaum, M. J. (1992) Isoform-specific subcellular targeting of glucose transporters in mouse fibroblasts.J. Cell Biol. 116:785–797.

    Google Scholar 

  • Hudson, A. W., Fingar, D. C., Seidner, G. A., Griffiths, G., Burke, B. and Birnbaum, M. J. (1993) Targeting of the “insulin-responsive” glucose transporter (GLUT4) to the regulated secretory pathway in PC12 cells.J. Cell Biol. 122:579–588.

    Google Scholar 

  • Jhun, B. H., Rampal, A. L., Liu, H., Lachaal, M. and Jung, C. Y. (1992) Effects of insulin on steady state kinetics of GLUT4 subcellular distribution in rat adipocytes. Evidence of constitutive GLUT4 recycling.J. Biol. Chem. 267:17710–17715.

    Google Scholar 

  • Larkin, J. M., Brown, M. S., Goldstein, J. L. and Anderson, R. G. W. (1983) Depletion of intracellular potassium arrests coated pit formation and receptor-mediated endocytosis in fibroblasts.Cell 33:273–285.

    Google Scholar 

  • Laurie, S. M., Cain, C. C., Lienhard, G. E., and Castle, J. D. (1993) Members of the VAMP family of synaptic vesicle proteins are components of the glucose transporter-containing vesicles from rat adipocytes.J. Biol. Chem. 268:19110–19117.

    Google Scholar 

  • Marsh, M., and Helenius, A. (1980) Adsorbtive endocytosis of Semliki Forest virus.J. Mol. Biol. 142:439–454.

    Google Scholar 

  • Marsh, E. W., Leopold, P. L., Jones, N. L. and Maxfield, F. R. (1995) Oligomerized transferrin receptors are selectively retained by a lumenal sorting signal in a long-lived endocytic recycling compartment.J. Cell Biol. 129:1509–1522.

    Google Scholar 

  • Mayor, S., Presley, J. F. and Maxfield, F. R. (1993) Sorting of membrane components from endosomes and subsequent recycling to the cell surface occurs by a bulk flow process.J. Cell Biol. 121:1257–1269.

    Google Scholar 

  • Mueckler, M. (1990) Family of glucose-transporter genes. Implications for glucose homeostatis and diabetes.Diabetes 39:6–11.

    Google Scholar 

  • Nuoffer, C. and Balch, W. E. (1994) GTPases: Multifunctional molecular switches regulating vesicular traffic.Annu. Rev. Biochem. 63:949–990.

    Google Scholar 

  • Pasternak, C. A., Whitaker-Dowling, P. A. and Widnell, C. C. (1988) Stress-induced increase of hexose transport as a novel index of cytopathic effects in virus-infected cells; role of the L protein in the action of vesicular stomatitis virus.Virology 166:379–386.

    Google Scholar 

  • Pasternak, C. A., Aiyathurai, J. E. J., Makinde, V., Davies, A., Baldwin, S. A., Konieczko, E. M. and Widnell, C. C. (1991) Regulation of glucose uptake by stressed cells.J. Cell Physiol 149:324–331.

    Google Scholar 

  • Presley, J. F., Mayor, S., Dunn, K. W., Johnson, L. S., McGraw, T. E. and Maxfield, F. R. (1993) The end2 mutation in CHO cells slows the exit of transferrin receptors from the recycling compartment but bulk membrane recycling is unaffected.J. Cell Biol. 122:1231–1241.

    Google Scholar 

  • Robinson, L. J., Pang, S., Harris, D. S., Heuser, J. and James, D. E. (1992) Translocation of the glucose transporter (GLUT4) to the cell surface in permeabilized 3T3-L1 adipocytes: effects of ATP, insulin, and GTPγS and localization of GLUT4 to clathrin lattices.J. Cell Biol. 117:1181–1196.

    Google Scholar 

  • Rothman, J. E. and Orci, L. (1992) Molecular dissection of the secretory pathway.Nature 355:409–415.

    Google Scholar 

  • Satoh, S., Nishimura, H., Clark, A. E., Kozka, I. J., Vannucci, S. J., Simpson, I. A., Quon, M. J., Cushman, S. W. and Holman, G. D. (1991) Use of bismannose photolabel to elucidate insulin-regulated GLUT4 subcellular trafficking kinetics in rat adipose cells. Evidence that exocytosis is a critical site of hormone action.J. Biol. Chem. 268:17820–17829.

    Google Scholar 

  • Simon, K. O., Whitaker-Dowling, P. A., Youngner, J. S. and Widnell, C. C. (1990a) Sequential disassembly of the cytoskeleton in BHK21 cells infected with vesicular stomatitis virus.Virology 177:289–297.

    Google Scholar 

  • Simon, K. O., Cardamone, J. J., Whitaker-Dowling, P. A., Younger, J. S., and Widnell, C. C. (1990b) Cellular mechanisms in the superinfection exclusion of vesicular stomatitis virus.Virology 177:375–379.

    Google Scholar 

  • Simpson, J. A. and Cushman, S. W. (1986) Hormonal regulation of mammalian glucose transport.Annu. Rev. Biochem. 55:1059–1089.

    Google Scholar 

  • Sviderskaya, E. V., Jazrawi, E., Baldwin, S. A., Widnell, C. C. and Pasternak, C. A. (1996) Cellular stress causes accumulation of the glucose transporter at the surface of cells independently of their insulin sensitivity.J. Membr. Biol. (in press).

  • Warren, A. P., James, M. H., Menzies, D. E., Widnell, C. C., Whitaker-Dowling, P. A. and Pasternak, C. A. (1986) Stress induces an increased hexose uptake in cultured cells.J. Cell. Physiol. 128:383–388.

    Google Scholar 

  • Warren, A. P. and Pasternak, C. A. (1989) Common pathway for the induction of hexose transport by insulin and stress:J. Cell. Physiol. 138:323–328.

    Google Scholar 

  • Widnell, C. C., Baldwin, S. A., Davies, A., Martin, S. and Pasternak, C. A. (1990) Cellular stress induces a redistribution of the glucose transporter.FASEB J. 4:1634–1637.

    Google Scholar 

  • Wilcox, D. K., Whitaker-Dowling, P. A., Youngner, J. S. and Widnell, C. C. (1983) Rapid inhibition of pinocytosis in BHK-21 cells following infection with vesicular stomatitis virus.J. Cell Biol. 97:1444–14451.

    Google Scholar 

  • Yang, J., Clark, A. E., Harrison, R., Kozka, I. J. and Holman, G. D. (1992) Trafficking of glucose transporters in 3T3-L1 cells.Biochem. J. 281:809–817.

    Google Scholar 

  • Yang, J. and Holman, G. D. (1993) Comparison of GLUT4 and GLUT1 subcellular trafficking in basal and stimulated 3T3-L1 cells.J. Biol. Chem. 268:4600–4603.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Widnell, C.C. Control of glucose transport by GLUT1: Regulated secretion in an unexpected environment. Biosci Rep 15, 427–443 (1995). https://doi.org/10.1007/BF01204347

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01204347

Key words

Navigation