Ligand-mediated Galectin-1 endocytosis prevents intraneural H2O2 production promoting F-actin dynamics reactivation and axonal re-growth.

QUINTÁ HR 1, WILSON C 2, GONZÁLES-BILLAULT C 2. PASQUINI LA 1 AND RABINOVICH GA 3, PASQUINI JM 1.

EXPERIMENTAL NEUROLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2016 vol. 283 p. 165 - 178

0014-4886

Axonal growth conecollapse following spinal cord injury (SCI) is promoted by semaphorin3A (Sema3A)signaling via PlexinA4 surface receptor. This signaling triggers anintracellular pathway that promotes an increase in hydrogen peroxide levels andfilamentous actin (F-actin) destabilization, inducing the inhibition of axonalre-growth. In this study, we successfully demonstrate that only Galectin-1(Gal-1) in its dimeric form, but not in its monomeric form, promotes a decreasein hydrogen peroxide levels and a repolimerization of F-actin in the growthcone and in the filopodium of neuron surfaces. To promote this decrease inintraneuronal hydrogen peroxide levels, Gal-1 need an intact carbohydraterecognition domain. Furthermore, Gal-1 promotes its own active ligand-mediated endocytosistogether with the PlexinA4 receptor via N-glycans complex (ligand forgalectins) interaction, leaving the neuronal surface less sensitive to Sema3Aeffects. In summary, our results suggest that Gal-1 in its dimeric form promotesa re-activation of actin cytoskeleton dynamics via the internalization of Gal-1together with PlexinA4. This mechanism might explain the full axonal re-growthprocess, a de novo formation ofsynapse clustering, axonal re-myelination and functional recovery of coordinatedlocomotor activities in an in vivoSCI model (acute and chronic).