title: Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury.
abstract: Following spinal cord injury (SCI), semaphorin 3A (Sema3A) prevents axonal regeneration through binding to the neuropilin-1 (NRP-1)/PlexinA4 receptor complex. Here, we show that galectin-1 (Gal-1), an endogenous glycan-binding protein, selectively bound to the NRP-1/PlexinA4 receptor complex in injured neurons through a glycan-dependent mechanism, interrupts the Sema3A pathway and contributes to axonal regeneration and locomotor recovery after SCI. Although both Gal-1 and its monomeric variant contribute to de-activation of microglia, only high concentrations of wild-type Gal-1 (which co-exists in a monomer-dimer equilibrium) bind to the NRP-1/PlexinA4 receptor complex and promote axonal regeneration. Our results show that Gal-1, mainly in its dimeric form, promotes functional recovery of spinal lesions by interfering with inhibitory signals triggered by Sema3A binding to NRP-1/PlexinA4 complex, supporting the use of this lectin for the treatment of SCI patients.
authors.affiliation: Departamento de Química Biológica, Instituto de Química y Físico Química Biológica, Universidad de Buenos Aires, Buenos Aires C1113AAD, Argentina.
authors.forename: H R
authors.initials: HR
authors.lastname: Quintá
authors.affiliation: Departamento de Química Biológica, Instituto de Química y Físico Química Biológica, Universidad de Buenos Aires, Buenos Aires C1113AAD, Argentina.
authors.forename: J M
authors.initials: JM
authors.lastname: Pasquini
authors.affiliation: 1] Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires C1428, Argentina [2] Laboratorio de Glicómica Funcional, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1428, Argentina.
authors.forename: G A
authors.initials: GA
authors.lastname: Rabinovich
authors.affiliation: Departamento de Química Biológica, Instituto de Química y Físico Química Biológica, Universidad de Buenos Aires, Buenos Aires C1113AAD, Argentina.
authors.forename: L A
authors.initials: LA
authors.lastname: Pasquini
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism / Q000627:therapeutic use; D018345:Mice, Knockout; D039942:Neuropilin-1 / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism; D012038:Regeneration; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000254:growth & development / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology / Q000628:therapy
chemical_list: D037483:Galectin 1; D037102:Lectins; D011134:Polysaccharides; C488217:Sema3a protein, mouse; D040121:Semaphorin-3A; D039942:Neuropilin-1