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

Goh, Choo-Peng, Putz, Ulrich, Howitt, Jason, Low, Ley-Hian, Gunnersen, Jenny, Bye, Nicole, Morganti-Kossmann, Cristia and Tan, Seong-Seng (2014) Nuclear trafficking of Pten after brain injury leads to neuron survival not death. Experimental Neurology, 252 37-46. doi:10.1016/j.expneurol.2013.11.017

Author Goh, Choo-Peng
Putz, Ulrich
Howitt, Jason
Low, Ley-Hian
Gunnersen, Jenny
Bye, Nicole
Morganti-Kossmann, Cristia
Tan, Seong-Seng
Title Nuclear trafficking of Pten after brain injury leads to neuron survival not death
Journal name Experimental Neurology   Check publisher's open access policy
ISSN 0014-4886
Publication date 2014
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.expneurol.2013.11.017
Open Access Status
Volume 252
Start page 37
End page 46
Total pages 10
Place of publication Maryland Heights, MO United States
Publisher Academic Press
Collection year 2015
Language eng
Abstract 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.
Keyword Ndfip1
Traumatic brain injury
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 27 Oct 2014, 17:05:36 EST by Sylvie Pichelin on behalf of Queensland Brain Institute