Neuronal activity-dependent ATP enhances the pro-growth effect of repair Schwann cell extracellular vesicles by increasing their miRNA-21 loading
Functional recovery after peripheral nerve injuries is critically dependent on axonal regeneration. Several autonomous and non-cell autonomous processes regulate axonal regeneration, including the activation of a growth-associated transcriptional program in neurons and the reprogramming of different...
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Frontiers Media S.A.
2022-09-01
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Series: | Frontiers in Cellular Neuroscience |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2022.943506/full |
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author | Cristian Saquel Cristian Saquel Romina J. Catalan Rodrigo Lopez-Leal Ramon A. Ramirez David Necuñir David Necuñir Ursula Wyneken Ursula Wyneken Christophe Lamaze Felipe A. Court Felipe A. Court Felipe A. Court |
author_facet | Cristian Saquel Cristian Saquel Romina J. Catalan Rodrigo Lopez-Leal Ramon A. Ramirez David Necuñir David Necuñir Ursula Wyneken Ursula Wyneken Christophe Lamaze Felipe A. Court Felipe A. Court Felipe A. Court |
author_sort | Cristian Saquel |
collection | DOAJ |
description | Functional recovery after peripheral nerve injuries is critically dependent on axonal regeneration. Several autonomous and non-cell autonomous processes regulate axonal regeneration, including the activation of a growth-associated transcriptional program in neurons and the reprogramming of differentiated Schwann cells (dSCs) into repair SCs (rSCs), triggering the secretion of neurotrophic factors and the activation of an inflammatory response. Repair Schwann cells also release pro-regenerative extracellular vesicles (EVs), but is still unknown whether EV secretion is regulated non-cell autonomously by the regenerating neuron. Interestingly, it has been described that nerve activity enhances axonal regeneration by increasing the secretion of neurotrophic factors by rSC, but whether this activity modulates pro-regenerative EV secretion by rSC has not yet been explored. Here, we demonstrate that neuronal activity enhances the release of rSC-derived EVs and their transfer to neurons. This effect is mediated by activation of P2Y receptors in SCs after activity-dependent ATP release from sensory neurons. Importantly, activation of P2Y in rSCs also increases the amount of miRNA-21 present in rSC-EVs. Taken together, our results demonstrate that neuron to glia communication by ATP-P2Y signaling regulates the content of SC-derived EVs and their transfer to axons, modulating axonal elongation in a non-cell autonomous manner. |
first_indexed | 2024-04-12T04:35:52Z |
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id | doaj.art-8b4e323fffbe4abe80d7406214df8527 |
institution | Directory Open Access Journal |
issn | 1662-5102 |
language | English |
last_indexed | 2024-04-12T04:35:52Z |
publishDate | 2022-09-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Cellular Neuroscience |
spelling | doaj.art-8b4e323fffbe4abe80d7406214df85272022-12-22T03:47:48ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022022-09-011610.3389/fncel.2022.943506943506Neuronal activity-dependent ATP enhances the pro-growth effect of repair Schwann cell extracellular vesicles by increasing their miRNA-21 loadingCristian Saquel0Cristian Saquel1Romina J. Catalan2Rodrigo Lopez-Leal3Ramon A. Ramirez4David Necuñir5David Necuñir6Ursula Wyneken7Ursula Wyneken8Christophe Lamaze9Felipe A. Court10Felipe A. Court11Felipe A. Court12Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, ChileInstitut Curie, PSL Research University, INSERM U1143, CNRS UMR 3666, Membrane Mechanics and Dynamics of Intracellular Signaling Laboratory, Paris, FranceCenter for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, ChileCenter for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, ChileCenter for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, ChileCenter for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, ChileGeroscience Center for Brain Health and Metabolism, Santiago, ChileFacultad de Medicina, Universidad de los Andes, Santiago, ChileCenter of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, ChileInstitut Curie, PSL Research University, INSERM U1143, CNRS UMR 3666, Membrane Mechanics and Dynamics of Intracellular Signaling Laboratory, Paris, FranceCenter for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, ChileGeroscience Center for Brain Health and Metabolism, Santiago, ChileBuck Institute for Research on Aging, Novato, CA, United StatesFunctional recovery after peripheral nerve injuries is critically dependent on axonal regeneration. Several autonomous and non-cell autonomous processes regulate axonal regeneration, including the activation of a growth-associated transcriptional program in neurons and the reprogramming of differentiated Schwann cells (dSCs) into repair SCs (rSCs), triggering the secretion of neurotrophic factors and the activation of an inflammatory response. Repair Schwann cells also release pro-regenerative extracellular vesicles (EVs), but is still unknown whether EV secretion is regulated non-cell autonomously by the regenerating neuron. Interestingly, it has been described that nerve activity enhances axonal regeneration by increasing the secretion of neurotrophic factors by rSC, but whether this activity modulates pro-regenerative EV secretion by rSC has not yet been explored. Here, we demonstrate that neuronal activity enhances the release of rSC-derived EVs and their transfer to neurons. This effect is mediated by activation of P2Y receptors in SCs after activity-dependent ATP release from sensory neurons. Importantly, activation of P2Y in rSCs also increases the amount of miRNA-21 present in rSC-EVs. Taken together, our results demonstrate that neuron to glia communication by ATP-P2Y signaling regulates the content of SC-derived EVs and their transfer to axons, modulating axonal elongation in a non-cell autonomous manner.https://www.frontiersin.org/articles/10.3389/fncel.2022.943506/fullSchwann cellextracellular vesiclesATPpurinergic receptorsaxonal growthaxonal regeneration |
spellingShingle | Cristian Saquel Cristian Saquel Romina J. Catalan Rodrigo Lopez-Leal Ramon A. Ramirez David Necuñir David Necuñir Ursula Wyneken Ursula Wyneken Christophe Lamaze Felipe A. Court Felipe A. Court Felipe A. Court Neuronal activity-dependent ATP enhances the pro-growth effect of repair Schwann cell extracellular vesicles by increasing their miRNA-21 loading Frontiers in Cellular Neuroscience Schwann cell extracellular vesicles ATP purinergic receptors axonal growth axonal regeneration |
title | Neuronal activity-dependent ATP enhances the pro-growth effect of repair Schwann cell extracellular vesicles by increasing their miRNA-21 loading |
title_full | Neuronal activity-dependent ATP enhances the pro-growth effect of repair Schwann cell extracellular vesicles by increasing their miRNA-21 loading |
title_fullStr | Neuronal activity-dependent ATP enhances the pro-growth effect of repair Schwann cell extracellular vesicles by increasing their miRNA-21 loading |
title_full_unstemmed | Neuronal activity-dependent ATP enhances the pro-growth effect of repair Schwann cell extracellular vesicles by increasing their miRNA-21 loading |
title_short | Neuronal activity-dependent ATP enhances the pro-growth effect of repair Schwann cell extracellular vesicles by increasing their miRNA-21 loading |
title_sort | neuronal activity dependent atp enhances the pro growth effect of repair schwann cell extracellular vesicles by increasing their mirna 21 loading |
topic | Schwann cell extracellular vesicles ATP purinergic receptors axonal growth axonal regeneration |
url | https://www.frontiersin.org/articles/10.3389/fncel.2022.943506/full |
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