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We used transgenic mice in which one or both GTPases were genetically ablated to investigate the role of RalGTPases in the Schwann cell (SC) response to nerve injury and repair. RalGTPases were dispensable for SC function in the naive uninjured state. Ablation of both RalA and RalB (but not individually) in SCs resulted in impaired axon remyelination and target reinnervation following nerve injury, which resulted in slowed recovery of motor function. Ral GTPases were localized to the leading lamellipodia in SCs and were required for the formation and extension of both axial and radial processes of SCs. These effects were dependent on interaction with the exocyst complex and impacted on the rate of SC migration and myelination. Our results show that RalGTPases are required for efficient nerve repair by regulating SC process formation, migration, and myelination, therefore uncovering a novel role for these GTPases.<\/jats:p>","DOI":"10.1083\/jcb.201811002","type":"journal-article","created":{"date-parts":[[2019,6,14]],"date-time":"2019-06-14T19:25:30Z","timestamp":1560540330000},"page":"2370-2387","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["RalGTPases contribute to Schwann cell repair after nerve injury via regulation of process formation"],"prefix":"10.1083","volume":"218","author":[{"given":"Jorge","family":"Galino","sequence":"first","affiliation":[{"name":"The Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Cervellini","sequence":"additional","affiliation":[{"name":"The Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Zhu","sequence":"additional","affiliation":[{"name":"The Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7362-7635","authenticated-orcid":true,"given":"Nina","family":"St\u00f6berl","sequence":"additional","affiliation":[{"name":"The Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meike","family":"H\u00fctte","sequence":"additional","affiliation":[{"name":"The Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence R.","family":"Fricker","sequence":"additional","affiliation":[{"name":"The Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9465-2936","authenticated-orcid":true,"given":"Garrett","family":"Lee","sequence":"additional","affiliation":[{"name":"The Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"McDermott","sequence":"additional","affiliation":[{"name":"The Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Lalli","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age-Related Diseases, King\u2019s College London, Guy\u2019s Campus, London, UK 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7996-2696","authenticated-orcid":true,"given":"David L.H.","family":"Bennett","sequence":"additional","affiliation":[{"name":"The Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2019,6,14]]},"reference":[{"key":"2023072315454797000_bib1","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/j.neuron.2012.06.021","article-title":"c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration","volume":"75","author":"Arthur-Farraj","year":"2012","journal-title":"Neuron."},{"key":"2023072315454797000_bib2","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.1016\/j.celrep.2017.08.064","article-title":"Changes in the Coding and Non-coding Transcriptome and DNA Methylome that Define the Schwann Cell Repair Phenotype after Nerve Injury","volume":"20","author":"Arthur-Farraj","year":"2017","journal-title":"Cell Reports."},{"key":"2023072315454797000_bib3","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1097\/00006534-198901000-00024","article-title":"Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat","volume":"83","author":"Bain","year":"1989","journal-title":"Plast. 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