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The anti-apoptotic protein ITA is essential for NGF-mediated survival of embryonic chick neurons

Nature Neuroscience volume 2, pages 978–983 (1999)Cite this article

Abstract

The avian ITA is homologous to the baculoviral and mammalian inhibitor of apoptosis (IAP) proteins, which can prevent apoptosis by inhibition of specific caspases. We investigated the role of ITA in embryonic chick sympathetic and dorsal root ganglionic neurons, which depend on nerve growth factor (NGF) for their survival. Within 6 hours, NGF upregulated ITA protein production more than 25-fold in sensory and sympathetic neurons. Overexpression of ITA in primary neurons supported survival of these cells in the absence of NGF, and ita antisense constructs inhibited NGF-mediated survival. Thus the induction of ITA expression seems to be an essential signaling event for survival of sympathetic and dorsal root ganglionic sensory neurons in response to NGF.

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Figure 1: Time course of NGF-induced upregulation of ITA in primary sensory and sympathetic neurons from developing chick embryos.
Figure 2: Morphology of primary embryonic chick dorsal root ganglionic sensory neurons after transfection with plasmids coding for ita, antisense ita, itaΔBIR, bcl-2 or lacZ.
Figure 3: Neuronal survival after transfection with control and ita expression plasmids.
Figure 4: ITA immundetection in transfected sensory neurons.
Figure 5: The ita antisense plasmid leads to reduction of ITA protein and ita mRNA content in PC-12 cells and primary neurons.

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Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft, SFB 465/TPA3 and grants To61/8-1 and To61/8-4. M.R.D. was supported by a Humboldt fellowship. We thank Austin Smith for comments and reading the manuscript and A. Kraiss and S. Klüpfel for technical assistance.

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  1. Stefan Wiese and Matthew R. Digby: The first two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Klinische Forschergruppe Neuroregeneration, University of Wuerzburg, Josef-Schneider-Str.11, Wuerzburg, 97080, Germany

    Stefan Wiese, Matthew R. Digby, Jennifer M. Gunnersen, Rudolf Götz, Geng Pei, Bettina Holtmann & Michael Sendtner

  2. Division of Animal Health, Commonwealth Scientific and Industrial Research Organisation, Private Bag 24, Geelong, 3220, Victoria, Australia

    John Lowenthal

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Correspondence to Michael Sendtner.

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Wiese, S., Digby, M., Gunnersen, J. et al. The anti-apoptotic protein ITA is essential for NGF-mediated survival of embryonic chick neurons. Nat Neurosci 2, 978–983 (1999). https://doi.org/10.1038/14777

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