dc.contributor.author
Jochner, Magdalena C. E.
dc.contributor.author
An, Junfeng
dc.contributor.author
Lättig-Tünnemann, Gisela
dc.contributor.author
Kirchner, Marieluise
dc.contributor.author
Dagane, Alina
dc.contributor.author
Dittmar, Gunnar
dc.contributor.author
Dirnagl, Ulrich
dc.contributor.author
Eickholt, Britta J.
dc.contributor.author
Harms, Christoph
dc.date.accessioned
2019-06-27T13:33:27Z
dc.date.available
2019-06-27T13:33:27Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/24947
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-2707
dc.description.abstract
Phosphatase and tensin homolog (PTEN) signalling might influence neuronal survival after brain ischemia. However, the influence of the less studied longer variant termed PTEN-L (or PTENα) has not been studied to date. Therefore, we examined the translational variant PTEN-L in the context of neuronal survival. We identified PTEN-L by proteomics in murine neuronal cultures and brain lysates and established a novel model to analyse PTEN or PTEN-L variants independently in vitro while avoiding overexpression. We found that PTEN-L, unlike PTEN, localises predominantly in the cytosol and translocates to the nucleus 10-20 minutes after glutamate stress. Genomic ablation of PTEN and PTEN-L increased neuronal susceptibility to oxygen-glucose deprivation. This effect was rescued by expression of either PTEN-L indicating that both PTEN isoforms might contribute to a neuroprotective response. However, in direct comparison, PTEN-L replaced neurons were protected against ischemic-like stress compared to neurons expressing PTEN. Neurons expressing strictly nuclear PTEN-L NLS showed increased vulnerability, indicating that nuclear PTEN-L alone is not sufficient in protecting against stress. We identified mutually exclusive binding partners of PTEN-L or PTEN in cytosolic or nuclear fractions, which were regulated after ischemic-like stress. GRB2-associated-binding protein 2, which is known to interact with phosphoinositol-3-kinase, was enriched specifically with PTEN-L in the cytosol in proximity to the plasma membrane and their interaction was lost after glutamate exposure. The present study revealed that PTEN and PTEN-L have distinct functions in response to stress and might be involved in different mechanisms of neuroprotection.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
neuroprotection
en
dc.subject
ischemic-like stress
en
dc.subject
phosphatase and tensin homolog (PTEN)
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Unique properties of PTEN-L contribute to neuroprotection in response to ischemic-like stress
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
3183
dcterms.bibliographicCitation.doi
10.1038/s41598-019-39438-1
dcterms.bibliographicCitation.journaltitle
Scientific Reports
dcterms.bibliographicCitation.originalpublishername
Nature Publishing Group
dcterms.bibliographicCitation.volume
9
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
30816308
dcterms.isPartOf.eissn
2045-2322