Alternative glucose uptake mediated by ß-catenin/RSK1 axis under stress stimuli in mammalian cells.

Cells adapt to stress conditions by increasing glucose uptake as cytoprotective strategy. The efficiency of glucose uptake is determined by the translocation of glucose transporters (GLUTs) from cytosolic vesicles to cellular membranes in many tissues and cells. GLUT translocation is tightly controlled by the activation of Tre-2/BUB2/CDC16 1 domain family 4 (TBC1D4) via its phosphorylation. The mechanisms of glucose uptake under stress conditions remain to be clarified. In this study, we surprisingly found that glucose uptake is apparently increased for the early response to three stress stimuli, glucose starvation and the exposure to lipopolysaccharide (LPS) or deoxynivalenol (DON). The stress-induced glucose uptake was mainly controlled by the increment of ß-catenin level and the activation of RSK1. Mechanistically, ß-catenin directly interacted with RSK1 and TBC1D4, acting as the scaffold protein to recruit activated RSK1 to promote the phosphorylation of TBC1D4. In addition, ß-catenin was further stabilized due to the inhibition of GSK3ß kinase activity which is caused by activated RSK1 phosphorylating GSK3ß at Ser9. In general, this triple protein complex consisting of ß-catenin, phosphorylated RSK1, and TBC1D4 were increased in the early response to these stress signals, and consequently, further promoted the phosphorylation of TBC1D4 to facilitate the translocation of GLUT4 to the cell membrane. Our study revealed that the ß-catenin/RSK1 axis contributed to the increment of glucose uptake for cellular adaption to these stress conditions, shedding new insights into cellular energy utilization under stress.

T-2 toxin and deoxynivalenol (DON) exert distinct effects on stress granule formation depending on altered activity of SIRT1.

The T-2 toxin and deoxynivalenol (DON), as the most concerned members of trichothecenes, induce cellular stress responses and various toxic effects. Stress granules (SGs) are rapidly formed in response to stress and play an important role in the cellular stress response. However, it is not known whether T-2 toxin and DON induce SG formation. In this study, we found that T-2 toxin induces SG formation, while DON surprisingly suppresses SG formation. Meanwhile, we discovered that SIRT1 co-localized with SGs and regulated SG formation by controlling the acetylation level of the SG nucleator G3BP1. Upon T-2 toxin, the acetylation level of G3BP1 increased, but the opposite change was observed upon DON. Importantly, T-2 toxin and DON affect the activity of SIRT1 via changing NAD+ level in a different manner, though the mechanism remains to be clarified. These findings suggest that the distinct effects of T-2 toxin and DON on SG formation are caused by changes in the activity of SIRT1. Furthermore, we found that SGs increase the cell toxicity of T-2 toxin and DON. In conclusion, our results reveal the molecular regulation mechanism of TRIs on SG formation and provide novel insights into the toxicological mechanisms of TRIs.

Current progress of PM-localized protein functions in jasmonate pathway.

Jasmonate (JA), a class of lipid-derived phytohormone, regulates diverse developmental processes and responses to abiotic or biotic stresses. The biosynthesis and signaling of JA mainly occur in various organelles, except for the plasma membrane (PM). Recently, several PM proteins have been reported to be associated with the JA pathway. This mini-review summarized the recent progress on the functional role of PM-localized proteins involved in JA transportation, JA-related defense responses, and JA-regulated endocytosis.

JA-Induced Endocytosis of AtRGS1 Is Involved in G-Protein Mediated JA Responses.

Arabidopsis heterotrimeric G proteins regulate diverse plant growth and defense processes by coupling to 7TM AtRGS1 proteins. Although G protein mutants display alterations in response to multiple plant hormones, the underlying mechanism by which G proteins participate in the regulation of hormone responses remains elusive. Here, we show that genetic disruption of Gα and Gß subunits results in reduced sensitivity to JA treatment. Furthermore, using confocal microscopy, VA-TIRFM, and FRET-FLIM, we provide evidence that stimulation by JA induces phosphorylation- and C-terminus-dependent endocytosis of AtRGS1, which then promotes dissociation of AtRGS1 from AtGPA1. In addition, SPT analysis reveals that JA treatment affects the diffusion dynamics of AtRGS1 and AtRGS1-ΔCt. Taken together, these findings suggest that the JA signal activates heterotrimeric G proteins through the endocytosis of AtRGS1 and dissociation of AtRGS1 from AtGPA1, thus providing valuable insight into the mechanisms of how the G protein system perceives and transduces phytohormone signals.