Regulation of Dishevelled and -catenin in rat skeletal muscle: an alternative exercise-induced GSK-3 signaling pathway

Aschenbach, William G., Richard C. Ho, Kei Sakamoto, Nobuharu Fujii, Yangfeng Li, Young-Bum Kim, Michael F. Hirshman, and Laurie J. Goodyear. Regulation of Dishevelled and -catenin in rat skeletal muscle: an alternative exercise-induced GSK-3 signaling pathway. Am J Physiol Endocrinol Metab 291: E152–E158, 2006. First published February 14, 2006; doi:10.1152/ajpendo.00180.2005.— catenin is a multifunctional protein involved in cell-cell adhesion and the Wnt signaling pathway. -Catenin is activated upon its dephosphorylation, an event triggered by Dishevelled (Dvl)-mediated phosphorylation and deactivation of glycogen synthase kinase-3 (GSK3 ). In skeletal muscle, both insulin and exercise decrease GSK-3 activity, and we tested the hypothesis that these two stimuli regulate -catenin. Immunoblotting demonstrated that Dvl, Axin, GSK-3 , and -catenin proteins are expressed in rat red and white gastrocnemius muscles. Treadmill running exercise in vivo significantly decreased -catenin phosphorylation in both muscle types, with complete dephosphorylation being elicited by maximal exercise. -Catenin dephosphorylation was intensity dependent, as dephosphorylation was highly correlated with muscle glycogen depletion during exercise (r 0.84, P 0.001). -Catenin dephosphorylation was accompanied by increases in GSK-3 Ser phosphorylation and Dvl-GSK-3 association. In contrast to exercise, maximal insulin treatment (1 U/kg body wt) had no effect on skeletal muscle -catenin phosphorylation or Dvl-GSK-3 interaction. In conclusion, exercise in vivo, but not insulin, increases the association between Dvl and GSK-3 in skeletal muscle, an event paralleled by -catenin dephosphorylation.