Cofilin dysregulation alters actin turnover in frataxin-deficient neurons
| العنوان: | Cofilin dysregulation alters actin turnover in frataxin-deficient neurons |
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| المؤلفون: | Francesc Palau, Belén Mollá, Federico V. Pallardo, Pilar Gonzalez-Cabo, Diana C. Muñoz-Lasso, Pablo Calap-Quintana, José Luis García-Giménez |
| المساهمون: | Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Fundación Ramón Areces, Generalitat Valenciana, Centro de Investigación Biomédica en Red Enfermedades Raras (España) |
| المصدر: | Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020) Scientific Reports Digital.CSIC. Repositorio Institucional del CSIC instname |
| بيانات النشر: | Nature Portfolio, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Cofilin 1, Ataxia, Science, Phosphatase, Growth Cones, Mutation, Missense, macromolecular substances, Immunofluorescence, Molecular neuroscience, Filamentous actin, Article, Actin-Related Protein 2-3 Complex, Mice, Mice, Neurologic Mutants, Phosphoserine, Ganglia, Spinal, Iron-Binding Proteins, medicine, Neurites, Phosphoprotein Phosphatases, Animals, Phosphorylation, Actin, Cells, Cultured, Peripheral neuropathies, Neurons, Multidisciplinary, biology, medicine.diagnostic_test, Microfilament Proteins, Cofilin, Actin cytoskeleton, Actins, Axons, Cell biology, Actin Cytoskeleton, Disease Models, Animal, nervous system, Friedreich Ataxia, Frataxin, biology.protein, Medicine, medicine.symptom, Protein Processing, Post-Translational |
| الوصف: | 10 páginas, 3 figuras. Contiene material suplementario accesible en: https://doi.org/10.1038/s41598-020-62050-7Test 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. Tis work was supported by grants from the Ministerio de Economía y Competitividad de España [Grant no. PI11/00678; SAF2015-66625-R] within the framework of the National R+ D+ I Plan and co-funded by the Instituto de Salud Carlos III (ISCIII)-Subdirección General de Evaluación y Fomento de la Investigación and FEDER funds; Fundación Ramón Areces (CIVP18A3899); the Generalitat Valenciana (ACOMP/2014/058; PROMETEO/2018/135). CIBERER is an initiative developed by the Instituto de Salud Carlos III in cooperative and translational research on rare diseases. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b0bf079744afed55d0942ff17d57f4b7Test https://doaj.org/article/1c2e1b48290849ff8db4190d1f6da79cTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b0bf079744afed55d0942ff17d57f4b7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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