p31 Deficiency Influences Endoplasmic Reticulum Tubular Morphology and Cell Survival

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

doi:info:doi/10.1128/MCB.01089-08

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このアイテムへのリンクには次のURLをご利用ください:http://hdl.handle.net/11094/23088

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タイトル	p31 Deficiency Influences Endoplasmic Reticulum Tubular Morphology and Cell Survival
著者	Uemura, Takefumi Uemura, Takefumi
	Sato, Takashi Sato, Takashi
	Aoki, Takehiro Aoki, Takehiro
	Yamamoto, Akitsugu Yamamoto, Akitsugu
	Okada, Tetsuya Okada, Tetsuya
	Hirai, Rika Hirai, Rika
	Harada, Reiko Harada, Reiko
	Mori, Kazutoshi Mori, Kazutoshi
	Tagaya, Mitsuo Tagaya, Mitsuo
	Harada, Akihiro Harada, Akihiro
抄録	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.
公開者	American Society for Microbiology
掲載誌名	Molecular and Cellular Biology
巻	29
号	7
開始ページ	1869
終了ページ	1881
刊行年月	2009-04
ISSN	02707306
NCID	AA10620925
DOI	info:doi/10.1128/MCB.01089-08
URL	http://hdl.handle.net/11094/23088
言語	英語
カテゴリ	学術雑誌論文 Journal Article

著者版フラグ	publisher
NII資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
dcmi資源タイプ	text
DCTERMS.bibliographicCitation	Molecular and Cellular Biology.29(7) P.1869-P.1881
DC.title	p31 Deficiency Influences Endoplasmic Reticulum Tubular Morphology and Cell Survival
DC.creator	Uemura, Takefumi
	Sato, Takashi
	Aoki, Takehiro
	Yamamoto, Akitsugu
	Okada, Tetsuya
	Hirai, Rika
	Harada, Reiko
	Mori, Kazutoshi
	Tagaya, Mitsuo
	Harada, Akihiro
DC.publisher	American Society for Microbiology
DC.language" scheme="DCTERMS.RFC1766	英語
DCTERMS.issued" scheme="DCTERMS.W3CDTF	2009-04
DC.identifier	info:doi/10.1128/MCB.01089-08
DC.identifier" scheme="DCTERMS.URI	http://hdl.handle.net/11094/23088
DCTERMS.abstract	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.
citation_title	p31 Deficiency Influences Endoplasmic Reticulum Tubular Morphology and Cell Survival
citation_author	Uemura, Takefumi
	Sato, Takashi
	Aoki, Takehiro
	Yamamoto, Akitsugu
	Okada, Tetsuya
	Hirai, Rika
	Harada, Reiko
	Mori, Kazutoshi
	Tagaya, Mitsuo
	Harada, Akihiro
citation_publisher	American Society for Microbiology
citation_language	英語
citation_date	2009-04
citation_journal_title	Molecular and Cellular Biology
citation_volume	29
citation_issue	7
citation_firstpage	1869
citation_lastpage	1881
citation_issn	02707306
citation_doi	info:doi/10.1128/MCB.01089-08
citation_public_url	http://hdl.handle.net/11094/23088

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