Ligand-mediated Galectin-1 endocytosis prevents intraneural H2O2 production promoting F-actin dynamics reactivation and axonal re-growth
Axonal growth cone collapse following spinal cord injury (SCI) is promoted by semaphorin3A (Sema3A) signaling via PlexinA4 surface receptor. This interaction triggers intracellular signaling events leading to increased hydrogen peroxide levels which in turn promote filamentous actin (F-actin) destab...
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todo:paper_00144886_v283_n_p165_Quinta2023-10-03T14:12:45Z Ligand-mediated Galectin-1 endocytosis prevents intraneural H2O2 production promoting F-actin dynamics reactivation and axonal re-growth Quintá, H.R. Wilson, C. Blidner, A.G. González-Billault, C. Pasquini, L.A. Rabinovich, G.A. Pasquini, J.M. Axonal growth Filamentous actin Galectin-1 Hydrogen peroxide PlexinA4 Semaphorin3A Spinal cord injury F actin galectin 1 glycan hydrogen peroxide neuropilin plexin plexin A4 semaphorin 3A unclassified drug actin filament actin polymerization animal cell animal experiment animal model Article cell surface controlled study convalescence disease model embryo endocytosis filopodium growth cone in vivo study internalization male molecular mechanics molecular recognition mouse nerve cell nerve fiber regeneration nonhuman priority journal rat remyelinization spinal cord injury synaptogenesis Axonal growth cone collapse following spinal cord injury (SCI) is promoted by semaphorin3A (Sema3A) signaling via PlexinA4 surface receptor. This interaction triggers intracellular signaling events leading to increased hydrogen peroxide levels which in turn promote filamentous actin (F-actin) destabilization and subsequent inhibition of axonal re-growth. In the current study, we demonstrated that treatment with galectin-1 (Gal-1), in its dimeric form, 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 promoted its own active ligand-mediated endocytosis together with the PlexinA4 receptor, through mechanisms involving complex branched N-glycans. In summary, our results suggest that Gal-1, mainly in its dimeric form, promotes re-activation of actin cytoskeleton dynamics via 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. Significance statement: Axonal regeneration is a response of injured nerve cells critical for nerve repair in human spinal cord injury. Understanding the molecular mechanisms controlling nerve repair by Galectin-1, may be critical for therapeutic intervention. Our results show that Galectin-1; in its dimeric form, interferes with hydrogen peroxide production triggered by Semaphorin3A. The high levels of this reactive oxygen species (ROS) seem to be the main factor preventing axonal regeneration due to promotion of actin depolymerization at the axonal growth cone. Thus, Galectin-1 administration emerges as a novel therapeutic modality for promoting nerve repair and preventing axonal loss. © 2016 Elsevier Inc. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00144886_v283_n_p165_Quinta |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Axonal growth Filamentous actin Galectin-1 Hydrogen peroxide PlexinA4 Semaphorin3A Spinal cord injury F actin galectin 1 glycan hydrogen peroxide neuropilin plexin plexin A4 semaphorin 3A unclassified drug actin filament actin polymerization animal cell animal experiment animal model Article cell surface controlled study convalescence disease model embryo endocytosis filopodium growth cone in vivo study internalization male molecular mechanics molecular recognition mouse nerve cell nerve fiber regeneration nonhuman priority journal rat remyelinization spinal cord injury synaptogenesis |
| spellingShingle |
Axonal growth Filamentous actin Galectin-1 Hydrogen peroxide PlexinA4 Semaphorin3A Spinal cord injury F actin galectin 1 glycan hydrogen peroxide neuropilin plexin plexin A4 semaphorin 3A unclassified drug actin filament actin polymerization animal cell animal experiment animal model Article cell surface controlled study convalescence disease model embryo endocytosis filopodium growth cone in vivo study internalization male molecular mechanics molecular recognition mouse nerve cell nerve fiber regeneration nonhuman priority journal rat remyelinization spinal cord injury synaptogenesis Quintá, H.R. Wilson, C. Blidner, A.G. González-Billault, C. Pasquini, L.A. Rabinovich, G.A. Pasquini, J.M. Ligand-mediated Galectin-1 endocytosis prevents intraneural H2O2 production promoting F-actin dynamics reactivation and axonal re-growth |
| topic_facet |
Axonal growth Filamentous actin Galectin-1 Hydrogen peroxide PlexinA4 Semaphorin3A Spinal cord injury F actin galectin 1 glycan hydrogen peroxide neuropilin plexin plexin A4 semaphorin 3A unclassified drug actin filament actin polymerization animal cell animal experiment animal model Article cell surface controlled study convalescence disease model embryo endocytosis filopodium growth cone in vivo study internalization male molecular mechanics molecular recognition mouse nerve cell nerve fiber regeneration nonhuman priority journal rat remyelinization spinal cord injury synaptogenesis |
| description |
Axonal growth cone collapse following spinal cord injury (SCI) is promoted by semaphorin3A (Sema3A) signaling via PlexinA4 surface receptor. This interaction triggers intracellular signaling events leading to increased hydrogen peroxide levels which in turn promote filamentous actin (F-actin) destabilization and subsequent inhibition of axonal re-growth. In the current study, we demonstrated that treatment with galectin-1 (Gal-1), in its dimeric form, 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 promoted its own active ligand-mediated endocytosis together with the PlexinA4 receptor, through mechanisms involving complex branched N-glycans. In summary, our results suggest that Gal-1, mainly in its dimeric form, promotes re-activation of actin cytoskeleton dynamics via 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. Significance statement: Axonal regeneration is a response of injured nerve cells critical for nerve repair in human spinal cord injury. Understanding the molecular mechanisms controlling nerve repair by Galectin-1, may be critical for therapeutic intervention. Our results show that Galectin-1; in its dimeric form, interferes with hydrogen peroxide production triggered by Semaphorin3A. The high levels of this reactive oxygen species (ROS) seem to be the main factor preventing axonal regeneration due to promotion of actin depolymerization at the axonal growth cone. Thus, Galectin-1 administration emerges as a novel therapeutic modality for promoting nerve repair and preventing axonal loss. © 2016 Elsevier Inc. |
| format |
JOUR |
| author |
Quintá, H.R. Wilson, C. Blidner, A.G. González-Billault, C. Pasquini, L.A. Rabinovich, G.A. Pasquini, J.M. |
| author_facet |
Quintá, H.R. Wilson, C. Blidner, A.G. González-Billault, C. Pasquini, L.A. Rabinovich, G.A. Pasquini, J.M. |
| author_sort |
Quintá, H.R. |
| title |
Ligand-mediated Galectin-1 endocytosis prevents intraneural H2O2 production promoting F-actin dynamics reactivation and axonal re-growth |
| title_short |
Ligand-mediated Galectin-1 endocytosis prevents intraneural H2O2 production promoting F-actin dynamics reactivation and axonal re-growth |
| title_full |
Ligand-mediated Galectin-1 endocytosis prevents intraneural H2O2 production promoting F-actin dynamics reactivation and axonal re-growth |
| title_fullStr |
Ligand-mediated Galectin-1 endocytosis prevents intraneural H2O2 production promoting F-actin dynamics reactivation and axonal re-growth |
| title_full_unstemmed |
Ligand-mediated Galectin-1 endocytosis prevents intraneural H2O2 production promoting F-actin dynamics reactivation and axonal re-growth |
| title_sort |
ligand-mediated galectin-1 endocytosis prevents intraneural h2o2 production promoting f-actin dynamics reactivation and axonal re-growth |
| url |
http://hdl.handle.net/20.500.12110/paper_00144886_v283_n_p165_Quinta |
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1807322569917857792 |