Generation of a glucose signal by the glucose sensors and its
transduction to the nucleus.
Valérie BRACHET, Hiaso MORIYA, Mark JOHNSTON
Genetics, Wash. U. School of Medicine, 660, S. Euclid , St Louis, MO
63110, USA
Binding of glucose to the glucose sensors Rgt2 and Snf3 generates a
signal that is transduced to the nucleus via the
SCFGrr1 ubiquitin-conjugating protein complex, where it
induces expression of several HXT genes by affecting the function
of the Rgt1 transcriptional repressor/activator. Rgt2 and Snf3 are
similar to glucose transporters but do not transport glucose. To learn
how they generate a signal, we identified RGT2 mutations that
cause constitutive production of a glucose signal. Nearly all of these
mutations affect amino acids conserved in glucose transporters and, when
placed in HXT1, prevent glucose transport, suggesting that they
freeze Rgt2 in its glucose-bound conformation. To lurn how the glucose
signal is transduced to Rgt1, we analyzed Std1 and Mth1, which interact
with the cytoplasmic tails of Snf3 and Rgt2 and play a role in
repression of HXT genes expression. In the absence of glucose,
Mth1 and Std1 interact with Rgt1 and inhibit its ability to activate
transcription. Addition of glucose causes SCFGrr1 to mediate
rapid degradation of Mth1 and Std1, thus freeing Rgt1 to activate
transcription. A conserved 23 amino acid sequence in the cytoplasmic
tails of Snf3 and Rgt2 is required for glucose signaling and for their
interaction with Mth1 and Std1. We believe that binding of glucose to
the glucose sensors transmits a conformational change to their
cytoplasmic tails which causes them to recruit Mth1 and Std1 and causes
SCFGrr1 to mark them for degradation.
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