Extracellular Galectin-3 Induces Accelerated Oligodendroglial Differentiation Through Changes in Signaling Pathways and Cytoskeleton Dynamics

LAURA THOMAS AND LAURA A. PASQUINI

MOLECULAR NEUROBIOLOGY

HUMANA PRESS INC

Año: 2018

0893-7648

Galectin-3 (Gal-3) is a chimeric protein structurally composed of unusual tandem repeats of proline and short glycine-rich segmentsfused onto a carbohydrate recognition domain. Our studies have previously demonstrated that Gal-3 drives oligodendrocyte (OLG)differentiation to control myelin integrity and function. The cytoskeleton plays a key role in OLG maturation: the initial stage ofOLG process extension requires dynamic actin filament assembly, while subsequent myelin wrapping coincides with the upregulationof actin disassembly proteins which are dependent on myelin basic protein (MPB) expression. In this context, the aim of thepresent work was to elucidate the mechanism by which recombinant Gal-3 (rGal-3) induces OLG maturation, giving specialattention to the actin cytoskeleton. Our results show that rGal-3 induced early actin filament assembly accompanied by Erk signalingdeactivation, which led to a decrease in the number of platelet-derived growth factor receptor α (PDGFRα)+ cells concomitantlywith an increase in the number of 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNPase)+ cells at 1 day of treatment (TD1), and Aktsignaling activation at TD1 and TD3. Strikingly, rGal-3 induced an accelerated shift from polymerized to depolymerized actinbetween TD3 and TD5, accompanied by a significant increase inMBP, gelsolin, Rac1, Rac1-GTP, and β-catenin expression at TD5.These results were strongly supported by assays using Erk 1/2 and Akt inhibitors, indicating that both pathways are key to rGal-3-mediated effects. Erk 1/2 inhibition in control-treated cells resembled an rGal-3 like state characterized by an increase in MBP, β-catenin, and gelsolin expression. In contrast, Akt inhibition in rGal-3-treated cells reducedMBP, β-catenin, and gelsolin expression,indicating a blockade of rGal-3 effects. Taken together, these results indicate that rGal-3 accelerates OLG maturation by modulatingsignaling pathways and protein expression which lead to changes in actin cytoskeleton dynamics.