Pancortin-2 interacts with WAVE1 and Bcl-xL in a mitochondria-associated protein complex that mediates ischemic neuronal death

Cheng, Aiwu, Arumugam, Thiruman, Liu, Dong, Khatri, Rina G., Mustafa, Khadija, Kwak, Seung, Ling, Huai-Ping, Gonzales, Cathleen, Xin, Ouyang, Jo, Dong-Gyu, Guo, Zhihong, Mark, Robert J. and Mattson, Mark P. (2007) Pancortin-2 interacts with WAVE1 and Bcl-xL in a mitochondria-associated protein complex that mediates ischemic neuronal death. Journal of Neuroscience, 27 7: 1519-1528. doi:10.1523/JNEUROSCI.5154-06.2007

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Author Cheng, Aiwu
Arumugam, Thiruman
Liu, Dong
Khatri, Rina G.
Mustafa, Khadija
Kwak, Seung
Ling, Huai-Ping
Gonzales, Cathleen
Xin, Ouyang
Jo, Dong-Gyu
Guo, Zhihong
Mark, Robert J.
Mattson, Mark P.
Title Pancortin-2 interacts with WAVE1 and Bcl-xL in a mitochondria-associated protein complex that mediates ischemic neuronal death
Journal name Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
1529-2401
Publication date 2007-02-01
Sub-type Article (original research)
DOI 10.1523/JNEUROSCI.5154-06.2007
Open Access Status File (Publisher version)
Volume 27
Issue 7
Start page 1519
End page 1528
Total pages 10
Place of publication Washington DC, United States
Publisher Society for Neuroscience
Language eng
Formatted abstract
The actin-modulating protein Wiskott-Aldrich syndrome protein verprolin homologous-1 (WAVE1) and a novel CNS-specific protein, pancortin, are highly enriched in adult cerebral cortex, but their functions are unknown. Here we show that WAVE1 and pancortin-2 interact in a novel cell death cascade in adult, but not embryonic, cerebral cortical neurons. Focal ischemic stroke induces the formation of a protein complex that includes pancortin-2, WAVE1, and the anti-apoptotic protein Bcl-xL. The three-protein complex is associated with mitochondria resulting in increased association of Bax with mitochondria, cytochrome c release, and neuronal apoptosis. In pancortin null mice generated using a Cre-loxP system, ischemia-induced WAVE1–Bcl-xL interaction is diminished, and cortical neurons in these mice are protected against ischemic injury. Thus, pancortin-2 is a mediator of ischemia-induced apoptosis of neurons in the adult cerebral cortex and functions in a novel mitochondrial/actin-associated protein complex that sequesters Bcl-xL.
Keyword pancortin
WAVE1
cerebral ischemia
stroke
neuronal cell death
Bcl-xL
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 27 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 17 Nov 2009, 22:21:14 EST