Galectin-3 Exerts a Pro-differentiating and Pro-myelinating Effect Within a Temporal Window Spanning Precursors and Pre-oligodendrocytes: Insights into the Mechanisms of Action

THOMAS, LAURA; PASQUINI, LAURA ANDREA; PASQUINI, LAURA ANDREA; THOMAS, LAURA

MOLECULAR NEUROBIOLOGY

HUMANA PRESS INC

Año: 2020 vol. 57 p. 976 - 987

0893-7648

Oligodendrocytes (OLG) are the cells resident in the CNS responsible for myelination. OLG undergo a succession of morphologicaland molecular changes along several maturational stages. Galectin-3 (Gal-3) is a 25- to 35-KDa protein belonging to thefamily of carbohydrate-binding galectins, which bind to glycoconjugates containing β-galactosides. Gal-3 lacks a specificreceptor and its binding is thus rather unspecific, as it depends on the cellular environment and the repertoire of glycomoleculesat the time when Gal-3 is present. Our previous work revealed that recombinant Gal-3 (rGal-3)?treated OLG showed accelerateddifferentiation, evidenced by an increase in the number of mature cells to the detriment of immature ones and accelerated actincytoskeleton dynamics. These changes were a consequence of rGal-3 influence on Akt, Erk 1/2, and β-catenin signalingpathways. Considering this previous evidence, the aim of this study was to identify the temporal window of rGal-3 action onthe OLG lineage to induce OLG maturation by using specific single pulses of rGal-3 over the different maturational stages ofOLG, and to unravel its main direct targets promoting OLG differentiation by mass spectrometry analysis. Our results reveal akey temporal window spanning between OPC and pre-OLG states in which rGal-3 action promotes OLG differentiation, andidentify several targets for rGal-3 binding including proteins related to the cytoskeleton, signaling pathways, metabolism andintracellular trafficking, among others. These results highlight the relevance of Gal-3 in signaling pathways regulating oligodendroglialdifferentiation and support a potential therapeutic role for rGal-3 in demyelinating diseases such as multiple sclerosis.