The Glycogen Synthase Kinase-3 in the Regulation of Ion Channels and Cellular Carriers

Glycogen synthase kinase-3 (GSK-3) is a highly evolutionarily conserved and ubiquitously expressed serine/threonine kinase, an enzyme protein profoundly specific for glycogen synthase (GS). GSK-3 is involved in various cellular functions and physiological processes, including cell proliferation, differentiation, motility, and survival as well as glycogen metabolism, protein synthesis, and apoptosis. There are two isoforms of human GSK-3 (named GSK-3α and GSK-3β) encoded by two distinct genes. Recently, GSK-3β has been reported to function as a powerful regulator of various transport processes across the cell membrane. This kinase, GSK-3β, either directly or indirectly, may stimulate or inhibit many different types of transporter proteins, including ion channel and cellular carriers. More specifically, GSK-3β-sensitive cellular transport regulation involves various calcium, chloride, sodium, and potassium ion channels, as well as a number of Na+-coupled cellular carriers including excitatory amino acid transporters EAAT2, 3 and 4, high-affinity Na+ coupled glucose carriers SGLT1, creatine transporter 1 CreaT1, and the type II sodium/phosphate cotransporter NaPi-IIa. The GSK-3β-dependent cellular transport regulations are a part of the kinase functions in numerous physiological and pathophysiological processes. Clearly, additional studies are required to examine the role of GSK-3β in many other types of cellular transporters as well as further elucidating the underlying mechanisms of GSK-3β-mediated cellular transport regulation.