Abstract
In yeast, glucose induction of HXT (glucose transporter gene) expression is achieved via the Rgt2 and Snf3 glucose sensing receptor (GSR)-mediated signal transduction pathway. The membrane-associated casein kinases Yck1 and Yck2 (Ycks) are involved in this pathway, but their exact role remains unclear. Previous work suggests that the Ycks are activated by the glucose-bound GSRs and transmit the glucose signal from the plasma membrane to the nucleus. However, here we provide evidence that the YCks are constitutively active and required for the stability of the Rgt2 receptor. Cell surface levels of Rgt2 are significantly decreased in a yck1Δyck2ts mutant, but this is not due to endocytosis-mediated vacuolar degradation of the receptor. Similar observations are made in an akr1Δ mutant, where the Ycks are no longer associated with the membrane, and in a sod1Δ mutant in which the kinases are unstable. Of note, in an akr1Δ mutant, both the Ycks and Rgt2 are mislocalized to the cytoplasm, where Rgt2 is stable and functions as an effective receptor for glucose signaling. We also demonstrate that Rgt2 is phosphorylated on the putative Yck consensus phosphorylation sites in its C-terminal domain (CTD) in a Yck-dependent manner and that this glucose-induced modification is critical for its stability and function. Thus, these results indicate a role for the Ycks in stabilizing Rgt2 and suggest that Rgt2 may use glucose binding as a molecular switch not to activate the Ycks but to promote Yck-dependent interaction and phosphorylation of the CTD that increases its stability.
Highlights
Glucose serves as both a fuel for energy and a precursor for the biosynthesis of cellular building blocks such as amino acids, fatty acids, and n ucleotides[1,2]
The yeast cells increase their glycolytic capacity, in part, by facilitating glucose uptake through glucose transporter (HXT) genes[9,10]. This is achieved through a glucose signaling pathway that begins at the cell surface with the glucose sensing receptors (GSRs) Rgt[2] and Snf[3] and ends in the nucleus with the Rgt[1] r epressor[11–14]
The Ycks are involved in the GSR-mediated glucose sensing and signaling, but their exact role remains unclear
Summary
Glucose serves as both a fuel for energy and a precursor for the biosynthesis of cellular building blocks such as amino acids, fatty acids, and n ucleotides[1,2]. The yeast cells increase their glycolytic capacity, in part, by facilitating glucose uptake through glucose transporter (HXT) genes[9,10] This is achieved through a glucose signaling pathway that begins at the cell surface with the glucose sensing receptors (GSRs) Rgt[2] and Snf[3] and ends in the nucleus with the Rgt[1] r epressor[11–14]. Many SCF substrates are phosphorylated prior to ubiquitination, and the plasma membrane-tethered casein kinases Yck[1] and Yck[2] ( referred to as Ycks), the homologs of the casein kinase 1-gamma (CK1γ), were shown to be responsible for the phosphorylation of Mth[1] and Std[119] These results led to the view that the Scientific Reports | (2022) 12:1598. As a signaling molecule, appears to play a key role in regulating cell surface levels of GSRs: Rgt[2] is expressed in the plasma membrane when glucose is abundant, turning on glucose signaling; it is endocytosed and degraded in the vacuole in response to glucose depletion, turning off s ignaling[25].
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