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OASIS, a CREB/ATF-family member, modulates UPR signalling in astrocytes

Nature Cell Biology volume 7, pages 186–194 (2005)Cite this article

Abstract

Endoplasmic reticulum (ER) stress transducers IRE1, PERK and ATF6 are well known to transduce signals from the ER to the cytoplasm and nucleus when unfolded proteins are accumulated in the ER. Here, we identified OASIS as a novel ER stress transducer. OASIS is a basic leucine zipper (bZIP) transcription factor of the CREB/ATF family with a transmembrane domain that allows it to associate with the ER. The molecule is cleaved at the membrane in response to ER stress, and its cleaved amino-terminal cytoplasmic domain, which contains the bZIP domain, translocates into the nucleus where it activates the transcription of target genes that are mediated by ER stress-responsive and cyclic AMP-responsive elements. Intriguingly, OASIS was induced at the transcriptional level during ER stress in astrocytes of the central nervous system, but not in other cell types examined. Furthermore, overexpression of OASIS resulted in induction of BiP and suppression of ER-stress-induced cell death, whereas knockdown partially reduced BiP levels and led to ER stress in susceptible astrocytes. Our results reveal pivotal roles for OASIS in modulating the unfolded protein response in astrocytes, and the possibility that cell type-specific UPR signalling also exists in other cells.

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Figure 1: OASIS is upregulated and cleaved at the transmembrane region in response to ER stress in astrocytes.
Figure 2: Activation of the BiP promoter by OASIS.
Figure 3: Effects of OASIS on CRE and ERSE sites.
Figure 4: Requirement for OASIS in the UPR signal and protective effects on ER stress-induced cell death.
Figure 5: OASIS expression after cryo-injury to the cortex.

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Acknowledgements

We thank K. Mori and Y. Omori for providing plasmids and antibodies, and M. Tohyama and S. Shiosaka for helpful discussions and critical reading of this manuscript. This work was partly supported by the UEHARA Foundation, and grants from the Japan Society for the Promotion of Science KAKENHI (14208093).

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Authors and Affiliations

  1. Department of Anatomy, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake, 889-1692, Miyazaki, Japan

    Shinichi Kondo, Tomohiko Murakami, Maiko Ogata, Soshi Kanemoto & Kazunori Imaizumi

  2. Division of Structural Cellular Biology, Nara Institute of Science and Technology (NAIST), 8916-5 Takayama, Ikoma, 630-0101, Nara, Japan

    Shinichi Kondo, Tomohiko Murakami, Maiko Ogata, Soshi Kanemoto & Kumi Otori

  3. Department of Anatomy, Nara Medical University, 840 Shijyo-cho, Kashihara, 634-8522, Nara, Japan

    Kouko Tatsumi & Akio Wanaka

  4. Department of Emergency Medicine, Yamagata University, School of Medicine, 2-2-2 Iidanishi, Yamagata city, 990-9585, Yamagata, Japan

    Ken Iseki

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  1. Shinichi Kondo
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Correspondence to Kazunori Imaizumi.

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Kondo, S., Murakami, T., Tatsumi, K. et al. OASIS, a CREB/ATF-family member, modulates UPR signalling in astrocytes. Nat Cell Biol 7, 186–194 (2005). https://doi.org/10.1038/ncb1213

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