| Budget Amount *help |
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 2005: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2004: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Research Abstract |
Membrane fusion within eukaryotic cells is mediated by SNAP receptors (SNAREs) that contain coiled-coil regions and are anchored with the apposed membranes. Syntaxin 18, a SNARE localized in the endoplasmic reticulum, is complexed with other three SNAREs (p31,BNIP1, and Sec22b) and peripheral membrane proteins, such as Sly1p,ZW10, and RINT-1. The syntaxin 18 complex is unique in that it contains cell cycle checkpoint proteins (ZW10 and RINT-1) and a proapoptotic protein (BNIP1). This study was aimed to reveal the function of syntaxin 18 and to gain insight into the mechanism of how the syntaxin 18 complex mediates cross-talk between membrane fusion, cell cycle control, and apoptosis. During the last two years, the following results were obtained.
1.Previous work showed that ZW10 and RINT-1 are associated with Rod and Rad50, respectively, in mitotic cells. We demonstrated that the amount of the syntaxin 18 complex comprising ZW10 and RINT-1 is constant throughout the cell cycle, suggesting that in mitotic cells, the syntaxin 18 complex is present as a complex distinct from ZW10-Rod and RINT-1-Rad50 complexes.
2.RINT-1 interacts with the N-terminal region of ZW10 and controls the localization and entry of ZW10 into the syntaxin 18 complex.
3.ZW10 is known to interact directly with dynamitin, a subunit of the dynein-dynactin complex that mediates cargo movement toward the minus-end of microtubules. In some cell lines, ZW10 was found to be localized not only in the ER but also in the Golgi apparatus, the latter of which is located near the minus-end of microtubules.
4.ZW10 was found to interact with subunits of coatomer that are components for COPI vesicles involved in anterograde transport.
5.BNIP1, which was originally characterized as a BH3-only protein, plays a role in ER membrane fusion.
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