Stimulation of Na+/K+ ATPase activity and Na+ coupled glucose transport by β-catenin.
β-Catenin is a multifunctional protein stimulating as oncogenic transcription factor several genes important for cell proliferation. β-Catenin-regulated genes include the serum- and glucocorticoid-inducible kinase SGK1, which is known to stimulate a variety of transport systems. The present study explored the possibility that β-catenin influences membrane transport. To this end, β-catenin was expressed in Xenopus oocytes with or without SGLT1 and electrogenic transport determined by dual electrode voltage clamp. As a result, expression of β-catenin significantly enhanced the ouabain-sensitive current of the endogeneous Na(+)/K(+)-ATPase. Inhibition of vesicle trafficking by brefeldin A revealed that the stimulatory effect of β-catenin on the endogenous Na(+)/K(+)-ATPase was not due to enhanced stability of the pump protein in the cell membrane. Expression of β-catenin further enhanced glucose-induced current (Ig) in SGLT1-expressing oocytes. In the absence of SGLT1 Ig was negligible irrespective of β-catenin expression. The stimulating effect of β-catenin on both Na(+)/K(+) ATPase and SGLT1 activity was observed even in the presence of actinomycin D, an inhibitor of transcription. The experiments disclose a completely novel function of β-catenin, i.e. the regulation of transport.
Sopjani
Mentor
M
Department of Physiology, University of Tübingen, Germany.
Alesutan
Ioana
I
Wilmes
Jan
J
Dërmaku-Sopjani
Miribane
M
Lam
Rebecca S
RS
Koutsouki
Evgenia
E
Jakupi
Muharrem
M
Föller
Michael
M
Lang
Florian
F
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D009865:Oocytes; D010042:Ouabain / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects; D014982:Xenopus laevis; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D019384:Nucleic Acid Synthesis Inhibitors; D051269:Sodium-Glucose Transporter 1; D051176:beta Catenin; D003609:Dactinomycin; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose