Cofilin dysregulation alters actin turnover in frataxin-deficient neurons

Abstract Abnormalities in actin cytoskeleton have been linked to Friedreich’s ataxia (FRDA), an inherited peripheral neuropathy characterised by an early loss of neurons in dorsal root ganglia (DRG) among other clinical symptoms. Despite all efforts to date, we still do not fully understand the mole...

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Autores principales:	Diana C. Muñoz-Lasso, Belén Mollá, Pablo Calap-Quintana, José Luis García-Giménez, Federico V. Pallardo, Francesc Palau, Pilar Gonzalez-Cabo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1c2e1b48290849ff8db4190d1f6da79c
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spelling	oai:doaj.org-article:1c2e1b48290849ff8db4190d1f6da79c2021-12-02T17:04:37ZCofilin dysregulation alters actin turnover in frataxin-deficient neurons10.1038/s41598-020-62050-72045-2322https://doaj.org/article/1c2e1b48290849ff8db4190d1f6da79c2020-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-62050-7https://doaj.org/toc/2045-2322Abstract Abnormalities in actin cytoskeleton have been linked to Friedreich’s ataxia (FRDA), an inherited peripheral neuropathy characterised by an early loss of neurons in dorsal root ganglia (DRG) among other clinical symptoms. Despite all efforts to date, we still do not fully understand the molecular events that contribute to the lack of sensory neurons in FRDA. We studied the adult neuronal growth cone (GC) at the cellular and molecular level to decipher the connection between frataxin and actin cytoskeleton in DRG neurons of the well-characterised YG8R Friedreich’s ataxia mouse model. Immunofluorescence studies in primary cultures of DRG from YG8R mice showed neurons with fewer and smaller GCs than controls, associated with an inhibition of neurite growth. In frataxin-deficient neurons, we also observed an increase in the filamentous (F)-actin/monomeric (G)-actin ratio (F/G-actin ratio) in axons and GCs linked to dysregulation of two crucial modulators of filamentous actin turnover, cofilin-1 and the actin-related protein (ARP) 2/3 complex. We show how the activation of cofilin is due to the increase in chronophin (CIN), a cofilin-activating phosphatase. Thus cofilin emerges, for the first time, as a link between frataxin deficiency and actin cytoskeleton alterations.Diana C. Muñoz-LassoBelén MolláPablo Calap-QuintanaJosé Luis García-GiménezFederico V. PallardoFrancesc PalauPilar Gonzalez-CaboNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Diana C. Muñoz-Lasso Belén Mollá Pablo Calap-Quintana José Luis García-Giménez Federico V. Pallardo Francesc Palau Pilar Gonzalez-Cabo Cofilin dysregulation alters actin turnover in frataxin-deficient neurons
description	Abstract Abnormalities in actin cytoskeleton have been linked to Friedreich’s ataxia (FRDA), an inherited peripheral neuropathy characterised by an early loss of neurons in dorsal root ganglia (DRG) among other clinical symptoms. Despite all efforts to date, we still do not fully understand the molecular events that contribute to the lack of sensory neurons in FRDA. We studied the adult neuronal growth cone (GC) at the cellular and molecular level to decipher the connection between frataxin and actin cytoskeleton in DRG neurons of the well-characterised YG8R Friedreich’s ataxia mouse model. Immunofluorescence studies in primary cultures of DRG from YG8R mice showed neurons with fewer and smaller GCs than controls, associated with an inhibition of neurite growth. In frataxin-deficient neurons, we also observed an increase in the filamentous (F)-actin/monomeric (G)-actin ratio (F/G-actin ratio) in axons and GCs linked to dysregulation of two crucial modulators of filamentous actin turnover, cofilin-1 and the actin-related protein (ARP) 2/3 complex. We show how the activation of cofilin is due to the increase in chronophin (CIN), a cofilin-activating phosphatase. Thus cofilin emerges, for the first time, as a link between frataxin deficiency and actin cytoskeleton alterations.
format	article
author	Diana C. Muñoz-Lasso Belén Mollá Pablo Calap-Quintana José Luis García-Giménez Federico V. Pallardo Francesc Palau Pilar Gonzalez-Cabo
author_facet	Diana C. Muñoz-Lasso Belén Mollá Pablo Calap-Quintana José Luis García-Giménez Federico V. Pallardo Francesc Palau Pilar Gonzalez-Cabo
author_sort	Diana C. Muñoz-Lasso
title	Cofilin dysregulation alters actin turnover in frataxin-deficient neurons
title_short	Cofilin dysregulation alters actin turnover in frataxin-deficient neurons
title_full	Cofilin dysregulation alters actin turnover in frataxin-deficient neurons
title_fullStr	Cofilin dysregulation alters actin turnover in frataxin-deficient neurons
title_full_unstemmed	Cofilin dysregulation alters actin turnover in frataxin-deficient neurons
title_sort	cofilin dysregulation alters actin turnover in frataxin-deficient neurons
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/1c2e1b48290849ff8db4190d1f6da79c
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Cofilin dysregulation alters actin turnover in frataxin-deficient neurons

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