Involvement of a novel Q-SNARE, D12, in quality control of the endomembrane system

Akiko Joo Okumura, Kiyotaka Hatsuzawa, Taku Tamura, Hisao Nagaya, Kazuko Saeki, Fumihiko Okumura, Kenji Nagao, Mitsuo Nishikawa, Akihiko Yoshimura, Ikuo Wada

研究成果: Article査読

22 被引用数 (Scopus)

抄録

The cellular endomembrane system requires the proper kinetic balance of synthesis and degradation of its individual components, which is maintained in part by a specific membrane fusion apparatus. In this study, we describe the molecular properties of D12, which was identified from a mouse expression library. This C-terminal anchored membrane protein has sequence similarity to both a yeast soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE), Use1p/Slt1p, and a recently identified human syntaxin 18-binding protein, p31. D12 formed a tight complex with syntaxin 18 as well as Sec22b and bound to α-SNAP, indicating that D12 is a SNARE protein. Although the majority of D12 is located in the endoplasmic reticulum and endoplasmic reticulum-Golgi intermediate compartments at steady state, overexpression or knockdown of D12 had no obvious effects on membrane trafficking in the early secretory pathway. However, suppression of D12 expression caused rapid appearance of lipofuscin granules, accompanied by apoptotic cell death without the apparent activation of the unfolded protein response. The typical cause of lipofuscin formation is the impaired degradation of mitochondria by lysosomal degradative enzymes, and, consistent with this, we found that proper post-Golgi maturation of cathepsin D was impaired in D12-deficient cells. This unexpected observation was supported by evidence that D12 associates with VAMP7, a SNARE in the endosomallysosomal pathway. Hence, we suggest that D12 participates in the degradative function of lysosomes.

本文言語English
ページ(範囲)4495-4506
ページ数12
ジャーナルJournal of Biological Chemistry
281
7
DOI
出版ステータスPublished - 2006 2月 17
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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