Extracellular Gal-3 induces oligodendroglial differentiation through the modulation of ERK and cytoskeleton pathways.

LAURA THOMAS AND LAURA A. PASQUINI

Paris

Congreso; Internatioanal Society for Neurochemistry and European Society for Neurochemistry; 2017

ISN

Galectin-3 (Gal-3), a chimeric protein structurally composed of unusual tandem repeats of proline and short glycine-rich segments fused onto a carbohydrate recognition domain, possesses multifaceted roles in physiological processes including the regulation of innate and adaptive immune responses. Our studies have previously demonstrated that recombinant Gal-3 (rGal-3) treatment accelerates oligodendrocyte (OLG) differentiation, and that a permissive glycophenotype to Gal-3 binding is only found in immature OLG. The cytoskeleton has been extensively shown to play a key role in OLG maturation and the morphological changes necessary to create fully mature OLG capable of myelination. Recent studies demonstrate that the initial stage of OLG process extension requires dynamic actin filament assembly, while subsequent myelin wrapping coincides with the upregulation of actin disassembly proteins which are dependent on MPB expression. The aim of our work is to elucidate the mechanism by which rGal3 expedites OLG maturation, giving special attention to the actin cytoskeleton. Our results show that, in primary rat OLG cultured in vitro in the presence of rGal-3 and with rGal-3 renewal every 48 hours, the total area of polymerized actin at 15?, 30? and 1 hour of treatment was greater than the area measured in OLG cultured in the absence of rGal-3. These changes were accompanied by a concomitant decrease in pERK at all times evaluated. At day in vitro 1 (DIV1), a decrease was observed in the polymerized actin area and in the number of PDGFRalpha+ cells in rGal-3-treated OLG, and an increase was detected in the number of CNPase+ cells, with no changes in the number of NG2+ and MBP+ cells. At DIV5, a decrease was observed in the polymerized actin area, accompanied by an increase in the number of MBP+ cells at the expense of a decrease in the number of PDGFRalpha+ and NG2+ cells. These results are in line with recently published data demonstrating that immature myelin sheaths with low levels of MBP have high levels of actin filaments, whereas more mature sheaths exhibit dramatically reduced actin filament levels. Results indicate that rGal-3 may favor OLG maturation by mediating the necessary changes in the actin cytoskeleton.