Reciprocal Encoding of Signal Intensity and Duration in a Glucose-Sensing Circuit

Abstract

SUMMARY Cells continuously adjust their behavior in response to changing environmental conditions. Both intensity and duration of external signals are critical factors in determining what response is initiated. To understand how intracellular signaling networks process such multidimensional information, we studied the AtRGS1-mediated glucose response system of Arabidopsis. By combining experiments with mathematical modeling, we discovered a reciprocal dose and duration response relying on the orchestrated action of three kinases (AtWNK1, AtWNK8, AtWNK10) acting on distinct time scales and activation thresholds. Specifically, we find that high concentrations of D-glucose rapidly signal through AtWNK8 and AtWNK10, whereas low, sustained sugar concentration slowly activate the pathway through AtWNK1, allowing the cells to respond similarly to transient, high-intensity signals, and sustained low-intensity signals. This “dose-duration reciprocity” allows encoding of both the intensity and persistence of glucose as an important energy resource and signaling molecule.

Arabidopsis Receptor of Activated C Kinase1 Phosphorylation by WITH NO LYSINE8 KINASE

“…The rack1a-2 mutant was hypersensitive to Glc (Fig. 7B), whereas wnk8-1 mutant was shown previously to be hyposensitive to Glc (Urano et al, 2012;Fu et al, 2014). These two opposing phenotypes of rack1a-2 and wnk8-1 single mutants provided an efficient way to determine the genetic relationship between rack1a-2 and wnk8-1.…”

A Tale of Two Sugars: Trehalose 6-Phosphate and Sucrose

“…Further convolutions can be expected from additional side effects of lowered Suc levels on the circadian clock (Haydon et al, 2013), phytohormones (Lilley et al, 2012;Sairanen et al, 2012), and micro-RNA156 signaling (Yang et al, 2013;Yu et al, 2013). Glc and Fru levels are also likely to be affected (Bihmidine et al, 2013), which will have an impact on hexose-sugar signaling pathways mediated by hexokinase (Moore et al, 2003), TOR (Dobrenel et al, 2013(Dobrenel et al, , 2016Xiong et al, 2013), or REGULATOR OF G-PROTEIN SIGNALING1 (Fu et al, 2014). It should also be noted that imposed changes in expression of SnRK1 can affect Tre6P and Suc levels, with both of these metabolites being increased when SnRK1 expression was suppressed in developing pea seeds (Radchuk et al, 2010).…”

Direct Modulation of Heterotrimeric G Protein-coupled Signaling by a Receptor Kinase Complex

“…Phosphorylation of GPCRs and AtRGS1 is necessary and sufficient for their endocytosis (5,6). In Arabidopsis, glucose-induced endocytosis of AtRGS1 is initiated by its transphosphorylation by three with no lysine (WNK) kinases (7,8). AtRGS1 endocytosis physically uncouples the GTPase-accelerating activity of AtRGS1 from the G␣ protein, allowing spontaneous nucleotide exchange and sustained activation (8).…”