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dc.contributor.author
Norrmén, Camilla
dc.contributor.author
Figlia, Gianluca
dc.contributor.author
Pfistner, Patrick
dc.contributor.author
Pereira, Jorge A.
dc.contributor.author
Bachofner, Sven
dc.contributor.author
Suter, Ueli
dc.date.accessioned
2018-12-20T10:13:37Z
dc.date.available
2018-05-30T03:59:47Z
dc.date.available
2018-06-13T14:42:06Z
dc.date.available
2018-12-20T10:13:37Z
dc.date.issued
2018-05-16
dc.identifier.issn
0270-6474
dc.identifier.issn
1529-2401
dc.identifier.other
10.1523/JNEUROSCI.3619-17.2018
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/266426
dc.identifier.doi
10.3929/ethz-b-000266426
dc.description.abstract
Schwann cells (SCs) are endowed with a remarkable plasticity. When peripheral nerves are injured, SCs dedifferentiate and acquire new functions to coordinate nerve repair as so-called repair SCs. Subsequently, SCs redifferentiate to remyelinate regenerated axons. Given the similarities between SC dedifferentiation/redifferentiation in injured nerves and in demyelinating neuropathies, elucidating the signals involved in SC plasticity after nerve injury has potentially wider implications. c-Jun has emerged as a key transcription factor regulating SC dedifferentiation and the acquisition of repair SC features. However, the upstream pathways that control c-Jun activity after nerve injury are largely unknown. We report that the mTORC1 pathway is transiently but robustly reactivated in dedifferentiating SCs. By inducible genetic deletion of the functionally crucial mTORC1-subunit Raptor in mouse SCs (including male and female animals), we found that mTORC1 reactivation is necessary for proper myelin clearance, SC dedifferentiation, and consequently remyelination, without major alterations in the inflammatory response. In the absence of mTORC1 signaling, c-Jun failed to be upregulated correctly. Accordingly, a c-Jun binding motif was found to be enriched in promoters of genes with reduced expression in injured mutants. Furthermore, using cultured SCs, we found that mTORC1 is involved in c-Jun regulation by promoting its translation, possibly via the eIF4F-subunit eIF4A. These results provide evidence that proper c-Jun elevation after nerve injury involves also mTORC1-dependent post-transcriptional regulation to ensure timely dedifferentiation of SCs.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Society for Neuroscience
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
differentiation
en_US
dc.subject
injury
en_US
dc.subject
mTOR
en_US
dc.subject
myelination
en_US
dc.subject
nerve
en_US
dc.subject
Schwann cells
en_US
dc.title
mTORC1 Is Transiently Reactivated in Injured Nerves to Promote c-Jun Elevation and Schwann Cell Dedifferentiation
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2018-05-16
ethz.journal.title
The Journal of Neuroscience
ethz.journal.volume
38
en_US
ethz.journal.issue
20
en_US
ethz.journal.abbreviated
JNeurosci
ethz.pages.start
4811
en_US
ethz.pages.end
4828
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Washington, DC
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::03367 - Suter, Ulrich / Suter, Ulrich
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02539 - Institut für Molecular Health Sciences / Institute of Molecular Health Sciences::03367 - Suter, Ulrich / Suter, Ulrich
ethz.date.deposited
2018-05-30T04:00:15Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-06-13T14:42:30Z
ethz.rosetta.lastUpdated
2024-02-02T06:52:38Z
ethz.rosetta.versionExported
true
ethz.COinS
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