Abstract
Jung et al . investigated enhancement of Na + ,K + -ATPase (adenosine triphosphatase) activity by the actin-binding protein cofilin and discovered a novel regulatory mechanism in which cofilin recruits the glycolytic enzyme triose-phosphate isomerase (TPI) to provide a ready supply of ATP. Na + ,K + -ATPase plays a crucial role in cell volume regulation and electrical signaling by using energy from the hydrolysis of ATP, preferentially derived from glycolysis, to maintain Na + and K + gradients across the cell membrane. Cofilin, which, when dephosphorylated, promotes actin filament turnover and thereby plays a role in cellular processes that depend on actin dynamics, interacts with Na + ,K + -ATPase and enhances its activity. Jung et al . used a yeast two-hybrid assay to screen a rat skeletal muscle cDNA library and discovered that cofilin interacted with TPI. The association of cofilin, TPI, and Na + ,K + -ATPase was confirmed in vivo both by immunofluorescence and by Western analysis of immunoprecipitates of HeLa cells transfected with labeled cofilin and labeled TPI. Pharmacological analysis indicated that activation of Rho signaling pathways resulted in translocation of cofilin and TPI to the cell membrane and increased association with Na + ,K + -ATPase. Activating Rho or overexpressing cofilin increased Na + ,K + -ATPase activity, as assessed by ouabain-sensitive 86 Rb + uptake. However, inhibiting the Rho pathway, or overexpressing cofilin-S3A, a mutant form that could not be phosphorylated, attenuated Na + ,K + -ATPase activity. Pharmacological analysis indicated that Rho pathway activation led to decreased [Na] i and confirmed the dependence of Na + ,K + -ATPase on glycolytic supplies of ATP, rather than ATP derived from oxidative phosphorylation. The data suggest a role for phosphorylated cofilin, and for Rho, in regulation of the Na + ,K + -ATPase. J. Jung, T. Yoon, E. C. Choi, K. Lee, Interaction of cofilin with triose-phosphate isomerase contributes glycolytic fuel for Na + ,K + -ATPase via Rho-mediated signaling pathway. J. Biol. Chem. 277 , 48931-48947 (2002). [Abstract] [Full Text]
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