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Neuroglobin promotes neurite outgrowth via differential binding to PTEN and Akt.

Authors: Li, L  Liu, QR  Xiong, XX  Liu, JM  Lai, XJ  Cheng, C  Pan, F  Chen, Y  Yu, SB  Yu, AC  Chen, XQ 
Citation: Li L, etal., Mol Neurobiol. 2014 Feb;49(1):149-62. doi: 10.1007/s12035-013-8506-7. Epub 2013 Aug 1.
Pubmed: (View Article at PubMed) PMID:23904011
DOI: Full-text: DOI:10.1007/s12035-013-8506-7

Neuroglobin, the third mammalian globin with a hexa-coordinated heme, exists predominantly in neurons of the brain. Neuroglobin plays an important role in neuronal death upon ischemia and oxidative stress. The physiological function of neuroglobin remains unclear. Here, we report a novel function of neuroglobin in neurite development. Knocking-down neuroglobin exhibited a prominent neurite-deficient phenotype in mouse neuroblastoma N2a cells. Silencing neuroglobin prevented neurite outgrowth, while ectopic expression of neuroglobin but not homologous cytoglobin promoted neurite outgrowth of N2a cells upon serum withdrawal. In primary cultured rat cerebral cortical neurons, neuroglobin was upregulated and preferentially distributed in neurites during neuronal development. Overexpression of neuroglobin but not cytoglobin in cultured cortical neurons promoted axonal outgrowth, while knocking-down of neuroglobin retarded axonal outgrowth. Neuroglobin overexpression suppressed phosphatase and tensin homolog (PTEN) but increased Akt phosphorylation during neurite induction. Bimolecular fluorescence complementation and glutathione S-transferase pull-down assays revealed that neuroglobin and various mutants (E53Q, E118Q, K119N, H64A, H64L, and Y44D) bound with Akt and PTEN differentially. Neuroglobin E53Q showed a prominent reduced PTEN binding but increased Akt binding, resulting in decreased p-PTEN, increased p-Akt, and increased neurite length. Taken together, we demonstrate a critical role of neuroglobin in neuritogenesis or development via interacting with PTEN and Akt differentially to activate phosphatidylinositol 3-kinase/Akt pathway, providing potential therapeutic applications of neuroglobin for axonopathy in neurological diseases.

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CRRD Object Information
CRRD ID: 9743968
Created: 2015-02-24
Species: All species
Last Modified: 2015-02-24
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.