Novel role of neuronal Ca2+ sensor-1 as a survival factor up-regulated in injured neurons

Tomoe Y. Nakamura, Andreas Jeromin, George Smith, Hideaki Kurushima, Hitoshi Koga, Yusaku Nakabeppu, Shigeo Wakabayashi, Junichi Nabekura

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45 Citations (Scopus)

Abstract

A molecular basis of survival from neuronal injury is essential for the development of therapeutic strategy to remedy neurodegenerative disorders. In this study, we demonstrate that an EF-hand Ca2+-binding protein neuronal Ca2+ sensor-1 (NCS-1), one of the key proteins for various neuronal functions, also acts as an important survival factor. Overexpression of NCS-1 rendered cultured neurons more tolerant to cell death caused by several kinds of stressors, whereas the dominant-negative mutant (E120Q) accelerated it. In addition, NCS-1 proteins increased upon treatment with glial cell line-derived neurotrophic factor (GDNF) and mediated GDNF survival signal in an Akt (but not MAPK)-dependent manner. Furthermore, NCS-1 is significantly up-regulated in response to axotomy-induced injury in the dorsal motor nucleus of the vagus neurons of adult rats in vivo, and adenoviral overexpression of E120Q resulted in a significant loss of surviving neurons, suggesting that NCS-1 is involved in an antiapoptotic mechanism in adult motor neurons. We propose that NCS-1 is a novel survival-promoting factor up-regulated in injured neurons that mediates the GDNF survival signal via the phosphatidylinositol 3- kinase-Akt pathway.

Original languageEnglish
Pages (from-to)1081-1091
Number of pages11
JournalJournal of Cell Biology
Volume172
Issue number7
DOIs
Publication statusPublished - Mar 2006

All Science Journal Classification (ASJC) codes

  • Cell Biology

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    Nakamura, T. Y., Jeromin, A., Smith, G., Kurushima, H., Koga, H., Nakabeppu, Y., Wakabayashi, S., & Nabekura, J. (2006). Novel role of neuronal Ca2+ sensor-1 as a survival factor up-regulated in injured neurons. Journal of Cell Biology, 172(7), 1081-1091. https://doi.org/10.1083/jcb.200508156