Figure 3.

Regulation of Tau phosphorylation levels by temperature and differentiation. Cold induces a decrease in BAG2 expression in undifferentiated cells, while the opposite is true in differentiated cells. Interestingly, while the decrease in BAG2 in undifferentiated cells results in an increase in levels of p-Tau (+p-Tau to +++pTau), the increase in BAG2 in differentiated cells has no change on p-Tau levels (++p-Tau to ++pTau). On cold condition, differentiation leads to a decrease in phosphorylated Tau (+++p-Tau to ++p-Tau), coincident with an increase in Tau phosphatase activity (very low to low) and a decrease in Tau kinase activity (moderate to low). Cold-induced inhibition of kinase and phosphatase activity results in a higher kinase-to-phosphatase activity in undifferentiated cells to differentiated cells. Cold treated undifferentiated cells have an increase in Tau phosphorylation due to a higher kinase activity and due to inhibition of BAG2 expression. In differentiated cells cold-attenuated kinase/phosphatase activity has no effect of p-Tau levels, while BAG2, while present, may be dependent on other temperature sensitive kinases.