p31 deficiency influences endoplasmic reticulum tubular morphology and cell survival

Takefumi Uemura, Takashi Sato, Takehiro Aoki, Akitsugu Yamamoto, Tetsuya Okada, Rika Hirai, Reiko Harada, Kazutoshi Mori, Mitsuo Tagaya, Akihiro Harada

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

p31, the mammalian orthologue of yeast Uselp, 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/)3/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.

Original languageEnglish
Pages (from-to)1869-1881
Number of pages13
JournalMolecular and Cellular Biology
Volume29
Issue number7
DOIs
StatePublished - Apr 2009
Externally publishedYes

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