Extracellular Galectin-3 induces accelerated oligodendroglial differentiation through changes in actin dynamics and Akt ? mTOR signalling pathway

LAURA THOMAS AND LAURA A. PASQUINI

Cordoba

Congreso; XXXIII Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN).; 2018

SAN

Galectin-3 (Gal-3) is a chimeric protein structurally composed ofunusual tandem repeats of proline and short glycine-rich segments fused onto acarbohydrate recognition domain. Our studies have previously demonstrated thatGal-3 drives oligodendrocyte (OLG) differentiation to control myelin integrityand function. The cytoskeleton playsa key role in OLG maturation: the initial stage of OLG process extensionrequires dynamic actin filament assembly, while subsequent myelin wrapping concurswith the upregulation of actin disassembly proteins which are dependent onmyelin basic protein (MPB) expression. In this context, the aim of the presentwork was to elucidate the mechanism by which recombinant Gal-3 (rGal-3) inducesOLG maturation, paying special attention to the actin cytoskeletonand Akt-mTOR signaling pathways. Immunocytochemistry results show thatrGal-3 induced early actin filament assembly together with a decrease in thenumber of platelet-derived growth factor receptor α (PDGFRα)+ cells and anincrease in the number of 2',3'-cyclic-nucleotide 3'-phosphodiesterase(CNPase)+ cells at 1 day of treatment (TD1). Furthermore, Western blotstudies revealed Akt signalling activation at TD1 and TD3, mTOR and mTORsubstrates 4EBP1 and p70SK6x phosphorylation, and Erk 1/2 deactivation at alltimes evaluated. Strikingly, rGal-3 induced an accelerated shift frompolymerized to depolymerized actin between TD3 and TD5, accompanied by asignificant increase in MBP, gelsolin, Rac1, Rac1-GTP, and β-catenin expressionat TD5. These results were strongly supported by assays using Erk 1/2, Akt andmTOR inhibitors, indicating that these pathways are key to rGal-3-mediatedeffects. Taken together, these results indicate that rGal-3 accelerates OLGmaturation by modulating signaling pathways and protein expression which leadto changes in actin cytoskeleton dynamics.