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

HR QUINTÁ; C WILSON; A BLIDNER; C GONZALEZ-BILLAULT; LA PASQUINI; GA RABINOVICH; JM PASQUINI

EXPERIMENTAL NEUROLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2016

0014-4886

Axonal growth cone collapse following spinal cord injury (SCI) is promoted by semaphorin3A (Sema3A) signaling via PlexinA4 surface receptor. This interaction triggers an intracellular pathway that induces an increase in hydrogen peroxide levels which promoted filamentous actin (F-actin) destabilization and, therefore, inhibition of axonal re-growth. In the current study, we demonstrated that treatment with galectin-1 (Gal-1), in its dimeric conformation, promotes a decrease in hydrogen peroxide (H2O2) levels and F-actin repolimerization in the growth cone and in the filopodium of neuron surfaces. This effect was dependent on the carbohydrate recognition activity of Gal-1, as it was prevented using a Gal-1 mutant lacking carbohydrate-binding activity. Furthermore, Gal-1 promotes its own active ligand-mediated endocytosis together with the PlexinA4 receptor, through mechanisms involving complex N-Glycans. In summary, our results suggest that Gal-1, in its dimeric conformation, promotes a re-activation of actin cytoskeleton dynamics via the internalization of the PlexinA4/Gal-1 complex. This mechanism could explain, at least in part, critical events in axonal regeneration including the full axonal re-growth process, de novo formation of synapse clustering, axonal re-myelination and functional recovery of coordinated locomotor activities in an in vivo acute and chronic SCI model.