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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Main Authors: Cristian Saquel, Romina J. Catalan, Rodrigo Lopez-Leal, Ramon A. Ramirez, David Necuñir, Ursula Wyneken, Christophe Lamaze, Felipe A. Court
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Cellular Neuroscience
Subjects:
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.
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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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