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Molecular and Cellular Biology, April 2009, p. 1869-1881, Vol. 29, No. 7
0270-7306/09/$08.00+0     doi:10.1128/MCB.01089-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

p31 Deficiency Influences Endoplasmic Reticulum Tubular Morphology and Cell Survival{triangledown}

Takefumi Uemura,1,2,{dagger} Takashi Sato,1,{dagger} Takehiro Aoki,2 Akitsugu Yamamoto,3 Tetsuya Okada,4 Rika Hirai,1 Reiko Harada,1 Kazutoshi Mori,4 Mitsuo Tagaya,2* and Akihiro Harada1,5*

Laboratory of Molecular Traffic, Department of Molecular and Cellular Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan,1 School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan,2 Department of Cell Biology, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan,3 Department of Biophysics, Graduate School of Science, Kyoto University, Sakyou-ku, Kyoto 606-8502, Japan,4 Department of Cell Biology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan5

Received 10 July 2008/ Returned for modification 4 September 2008/ Accepted 10 January 2009

p31, the mammalian orthologue of yeast Use1p, is an endoplasmic reticulum (ER)-localized soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) that forms a complex with other SNAREs, particularly syntaxin 18. However, the role of p31 in ER function remains unknown. To determine the role of p31 in vivo, we generated p31 conditional knockout mice. We found that homozygous deletion of the p31 gene led to early embryonic lethality before embryonic day 8.5. Conditional knockout of p31 in brains and mouse embryonic fibroblasts (MEFs) caused massive apoptosis accompanied by upregulation of ER stress-associated genes. Microscopic analysis showed vesiculation and subsequent enlargement of the ER membrane in p31-deficient cells. This type of drastic disorganization in the ER tubules has not been demonstrated to date. This marked change in ER structure preceded nuclear translocation of the ER stress-related transcription factor C/EBP homologous protein (CHOP), suggesting that ER stress-induced apoptosis resulted from disruption of the ER membrane structure. Taken together, these results suggest that p31 is an essential molecule involved in the maintenance of ER morphology and that its deficiency leads to ER stress-induced apoptosis.

* Corresponding author. Mailing address for Mitsuo Tagaya: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Hachioji, Tokyo 192-0392, Japan. Phone: 81-426-76-5419. Fax: 81-426-76-5468. E-mail: tagaya{at}ls.toyaku.ac.jp. Mailing address for Akihiro Harada: Laboratory of Molecular Traffic, Department of Molecular and Cellular Biology, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa, Maebashi, Gunma 371-8512, Japan. Phone: 81-27-220-8840. Fax: 81-27-220-8844. E-mail: aharada{at}showa.gunma-u.ac.jp

{triangledown} Published ahead of print on 2 February 2009.

{dagger} These two authors contributed equally to this work.

Molecular and Cellular Biology, April 2009, p. 1869-1881, Vol. 29, No. 7
0270-7306/09/$08.00+0     doi:10.1128/MCB.01089-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Aoki, T., Ichimura, S., Itoh, A., Kuramoto, M., Shinkawa, T., Isobe, T., Tagaya, M. (2009). Identification of the Neuroblastoma-amplified Gene Product as a Component of the Syntaxin 18 Complex Implicated in Golgi-to-Endoplasmic Reticulum Retrograde Transport. Mol. Biol. Cell 20: 2639-2649 [Abstract] [Full Text]  
  • Iinuma, T., Aoki, T., Arasaki, K., Hirose, H., Yamamoto, A., Samata, R., Hauri, H.-P., Arimitsu, N., Tagaya, M., Tani, K. (2009). Role of syntaxin 18 in the organization of endoplasmic reticulum subdomains. J. Cell Sci. 122: 1680-1690 [Abstract] [Full Text]  


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