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Nuclear trafficking of Pten after brain injury leads to neuron survival not death

journal contribution
posted on 2023-05-19, 13:15 authored by Goh, CP, Putz, U, Howitt, J, Low, LH, Gunnersen, J, Nicole ByeNicole Bye, Morganti-Kossman, C, Tan, SS
There is controversy whether accumulation of the tumor suppressor PTEN protein in the cell nucleus under stress conditions such as trauma and stroke causes cell death. A number of in vitro studies have reported enhanced apoptosis in neurons possessing nuclear PTEN, with the interpretation that its nuclear phosphatase activity leads to reduction of the survival protein phospho-Akt. However, there have been no in vivo studies to show that nuclear PTEN in neurons under stress is detrimental. Using a mouse model of injury, we demonstrate here that brain trauma altered the nucleo-cytoplasmic distribution of Pten, resulting in increased nuclear Pten but only in surviving neurons near the lesion. This event was driven by Ndfip1, an adaptor and activator of protein ubiquitination by Nedd4 E3 ligases. Neurons next to the lesion with nuclear PTEN were invariably negative for TUNEL, a marker for cell death. These neurons also showed increased Ndfip1 which we previously showed to be associated with neuron survival. Biochemical assays revealed that overall levels of Pten in the affected cortex were unchanged after trauma, suggesting that Pten abundance globally had not increased but rather Pten subcellular location in affected neurons had changed. Following experimental injury, the number of neurons with nuclear Pten was reduced in heterozygous mice (Ndfip1+/−) although lesion volumes were increased. We conclude that nuclear trafficking of Pten following injury leads to neuron survival not death.


Publication title

Experimental neurology








School of Pharmacy and Pharmacology


Academic Press Inc Elsevier Science

Place of publication

San Diego

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© 2013 Elsevier Inc. All rights reserved.

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