Abstract
Glycogen synthase kinase 3 (GSK3) was initially isolated as a critical protein in energy metabolism. However, subsequent studies indicate that GSK-3 is a multi-tasking kinase that links numerous signaling pathways in a cell and plays a vital role in the regulation of many aspects of cellular physiology. As a regulator of actin and tubulin cytoskeleton, GSK3 influences processes of cell polarization, interaction with the extracellular matrix, and directional migration of cells and their organelles during the growth and development of an animal organism. In this review, the roles of GSK3–cytoskeleton interactions in brain development and pathology, migration of healthy and cancer cells, and in cellular trafficking of mitochondria will be discussed.
Highlights
Glycogen synthase kinase-3 (GSK3) is a serine/threonine kinase
GSK3β can be activated in response to environmental conditions fluctuations, lack of trophic factors, cellular stress, which leads to increased apoptosis in mature cells [94,95,96]
It has been shown that GSK3β phosphorylation of the transcription factor CCAAT/enhancerbinding protein delta (CEBPD) in astrocytes was responsible for these processes, and that inhibition of GSK3β by LiCl attenuated murine microglia migration [101]
Summary
Glycogen synthase kinase-3 (GSK3) is a serine/threonine kinase. It was initially identified as a regulator (inhibitor) of glycogen synthesis [1]. In the still-increasing list of GSK3 substrates, there are, among others, proteins engaged in the regulation of actin cytoskeleton dynamics (e.g., Rho family members and related GTPases), microtubule-associated proteins (MAPs, e.g., Tau and collapsin response mediator protein 2 (CRMP 2)) and adhesion of cells to extracellular matrix (e.g., focal adhesion kinase, FAK) [8,9,10]. Acting through these substrates, GSK3 can influence cell polarization and directional migration, as well as intracellular trafficking of mitochondria and vesicular structures. This review discusses the key roles of GSK3-to-cytoskeleton and GSK3-to-extracellular matrix signaling in the brain, cardiac, and cancer cells, in normal and pathological settings
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