Dual function of the PI3K-Akt-mTORC1 axis in myelination of the peripheral nervous system Article Swipe
Gianluca Figlia
,
Camilla Norrmén
,
Jorge A. Pereira
,
Daniel Gerber
,
Ueli Suter
·
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.7554/elife.29241
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.7554/elife.29241
Myelination is a biosynthetically demanding process in which mTORC1, the gatekeeper of anabolism, occupies a privileged regulatory position. We have shown previously that loss of mTORC1 function in Schwann cells (SCs) hampers myelination. Here, we genetically disrupted key inhibitory components upstream of mTORC1, TSC1 or PTEN, in mouse SC development, adult homeostasis, and nerve injury. Surprisingly, the resulting mTORC1 hyperactivity led to markedly delayed onset of both developmental myelination and remyelination after injury. However, if mTORC1 was hyperactivated after myelination onset, radial hypermyelination was observed. At early developmental stages, physiologically high PI3K-Akt-mTORC1 signaling suppresses expression of Krox20 (Egr2), the master regulator of PNS myelination. This effect is mediated by S6K and contributes to control mechanisms that keep SCs in a not-fully differentiated state to ensure proper timing of myelination initiation. An ensuing decline in mTORC1 activity is crucial to allow myelination to start, while remaining mTORC1 activity drives myelin growth.
Related Topics
Concepts
mTORC1
PI3K/AKT/mTOR pathway
RHEB
Neuroscience
Biology
PTEN
Remyelination
Protein kinase B
TSC2
Regulator
TSC1
Myelin
Cell biology
Signal transduction
Central nervous system
Genetics
Gene
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.7554/elife.29241
- OA Status
- gold
- Cited By
- 118
- References
- 78
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2753363275
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2753363275Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.7554/elife.29241Digital Object Identifier
- Title
-
Dual function of the PI3K-Akt-mTORC1 axis in myelination of the peripheral nervous systemWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2017Year of publication
- Publication date
-
2017-09-06Full publication date if available
- Authors
-
Gianluca Figlia, Camilla Norrmén, Jorge A. Pereira, Daniel Gerber, Ueli SuterList of authors in order
- Landing page
-
https://doi.org/10.7554/elife.29241Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.7554/elife.29241Direct OA link when available
- Concepts
-
mTORC1, PI3K/AKT/mTOR pathway, RHEB, Neuroscience, Biology, PTEN, Remyelination, Protein kinase B, TSC2, Regulator, TSC1, Myelin, Cell biology, Signal transduction, Central nervous system, Genetics, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
118Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 8, 2024: 29, 2023: 6, 2022: 21, 2021: 17Per-year citation counts (last 5 years)
- References (count)
-
78Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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