Saltar al contenido
MilliporeSigma

Unique properties of PTEN-L contribute to neuroprotection in response to ischemic-like stress.

Scientific reports (2019-03-01)
Magdalena C E Jochner, Junfeng An, Gisela Lättig-Tünnemann, Marieluise Kirchner, Alina Dagane, Gunnar Dittmar, Ulrich Dirnagl, Britta J Eickholt, Christoph Harms
RESUMEN

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.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Roche
cOmplete, combinación de inhibidores de proteasas sin EDTA, Tablets provided in EASYpacks
Sigma-Aldrich
Anti-PTEN-alpha Antibody, clone 3A4.1, clone 3A4.1, from mouse
Sigma-Aldrich
Anti-GAB2 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody