The ubiquitous glucose transporter GLUT-1 belongs to the glucose-regulated protein family of stress-inducible proteins

Efrat Wertheimer*, Shlomo Sasson, Erol Cerasi, Yinon Ben-Neriah

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

174 Scopus citations

Abstract

In mammals, glucose transport is mediated by five structurally related glucose transporters that show a characteristic cell-specific expression. However, the rat brain/HepG2/erythrocyte-type glucose transporter GLUT-1 is expressed at low levels in most cells. The reason for this compression is not clear. GLUT-1 is negatively regulated by glucose. Another family of proteins, glucose-regulated proteins (GRPs), is also ubiquitously expressed and stimulated by glucose deprivation and other cellular stresses. We therefore hypothesized that GLUT-1 may be a glucose-regulated stress protein. This was tested by subjecting L8 myocytes and NIH 3T3 fibroblasts to glucose starvation or exposure to the calcium ionophore A23187, 2-mercaptoethanol, or tunicamycin, all known to increase GRP levels. The mRNA for GLUT-1 was augmented by 50-300% in a time-dependent manner, similarly to the changes in GRP-78 mRNA. Ex vivo incubation of rat soleus muscles induced a marked and concomitant rise in the mRNA levels of GLUT-1 and GRP-78. Finally, calcium ionophore A23187 and 2-mercaptoethanol induced a 2- to 3-fold increase in the levels of the GLUT-1 protein and hexose uptake. In all instances in which GRP-78 and GLUT-1 responded to stress, the transcription of the cell-specific muscle/adipocyte-type insulin-responsive glucose transporter (GLUT-4) did not change. Thus, despite the lack of structural similarity, GLUT-1 and GRP-78 expression is regulated similarly, whereas the regulation of GLUT-4, which is structurally related to GLUT-1, is different. We propose that GLUT-1 belongs to the GRP family of stress proteins and that its ubiquitous expression may serve a specific purpose during cellular stress.

Original languageAmerican English
Pages (from-to)2525-2529
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number6
StatePublished - 1991

Keywords

  • Cellular stress response

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