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

Research output: Contribution to journalArticle

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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 1 2006

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Glial Cell Line-Derived Neurotrophic Factor
Neurons
Phosphatidylinositol 3-Kinase
EF Hand Motifs
Axotomy
Wounds and Injuries
Motor Neurons
Neurodegenerative Diseases
Carrier Proteins
Proteins
Cell Death
Therapeutics

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Nakamura, T. Y., Jeromin, A., Smith, G., Kurushima, H., Koga, H., Nakabeppu, Y., ... 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

Novel role of neuronal Ca2+ sensor-1 as a survival factor up-regulated in injured neurons. / Nakamura, Tomoe Y.; Jeromin, Andreas; Smith, George; Kurushima, Hideaki; Koga, Hitoshi; Nakabeppu, Yusaku; Wakabayashi, Shigeo; Nabekura, Junichi.

In: Journal of Cell Biology, Vol. 172, No. 7, 01.03.2006, p. 1081-1091.

Research output: Contribution to journalArticle

Nakamura, TY, 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, vol. 172, no. 7, pp. 1081-1091. https://doi.org/10.1083/jcb.200508156
Nakamura, Tomoe Y. ; Jeromin, Andreas ; Smith, George ; Kurushima, Hideaki ; Koga, Hitoshi ; Nakabeppu, Yusaku ; Wakabayashi, Shigeo ; Nabekura, Junichi. / Novel role of neuronal Ca2+ sensor-1 as a survival factor up-regulated in injured neurons. In: Journal of Cell Biology. 2006 ; Vol. 172, No. 7. pp. 1081-1091.
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