Cross-talk between membrane fusion, cell cycle, and apoptosis

膜融合、细胞周期和细胞凋亡之间的串扰

基本信息

批准号：
14380339
负责人：
TAGAYA Mitsuo
金额：
$ 9.22万
依托单位：
Tokyo University of Pharmacy and Life Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14380339/
关键词：
Endoplasmic reticulum Membrane fusion Vesicular transport Cell cycle Apoptosis

项目摘要

The NSF-α-SNAP-SNAREs complex is a large protein complex implicated in membrane fusion between transport vesicles and their target membranes. We have recently discovered an endoplasmic reticulum (ER) SNARE, syntaxin 18, and demonstrated that this protein forms a complex with ZW10 (a kinetochore protein involved in spindle checkpoint), RINT-1 (G2/M checkpoint protein), and BNIP1 (a member of the pro-apoptotic BH3-only family). The purpose of this research is to elucidate the mechanisms underlying cross-talk between membrane fusion, cell-cycle, and apoptosis via the syntaxin 18 complex. The following results have been obtained.1)Interactions between components of the syntaxin 18 complexTwo-hybrid analysis revealed the interactions between syntaxin 18 and p31, RINT-1 and ZW10, and RINT-1 and BNIP1. RINT-1, ZW10 and p31 form a sub-complex.2)Involvement of ZW10 in membrane traffic between the ER and GolgiOverexpression, knockdown, and microinjection studies revealed that ZW10 in the interphase plays a role in membrane trafficking between the ER and Golgi.3)Implication of BNIP1 in ER-ER membrane fusionBNIP1 was found to participate in ER-ER membrane fusion, rather than membrane transport between the ER and Golgi. Binding studies revealed that Leu-114, a highly conserved residue in the pro-apoptotic BH3 domain of BNIP1, is essential for the interaction with α-SNAP but not with RINT-1. Overexpression of α-SNAP markedly delayed staurosporine-induced apoptosis. These results raise the possibility that BNIP1 functions in cross-talk between membrane fusion and apoptosis.

NSF-α-SNAP-SNARES复合物是一种在运输蔬菜与目标膜之间膜融合中隐含的大蛋白质复合物。我们最近发现了一种内质网（ER）SNARE，Syntaxin 18，并证明该蛋白与ZW10（旋转检查点涉及的动力学蛋白），RINT-1（G2/M CheckPoint蛋白）和BNIP1形成复合物。这项研究的目的是阐明通过语法18复合物在膜融合，细胞周期和凋亡之间的串扰的机制。已经获得了以下结果。1）语法18 complextwo-Hybrid分析之间的相互作用揭示了语法素18和p31，rint-1和zw10，以及rint-1和bnip1之间的相互作用。 RINT-1，ZW10和p31形成一个子复合物.2）ZW10参与ER和GolgioVerverse，敲低，敲低和显微注射研究之间的膜流量，表明ZW10在eR和Golgi.3中的膜交通中的膜交通在ER-ER-3）中的含量在ER-ER-ER-ER-ER-ERBN中起作用。融合，而不是ER和高尔基体之间的膜运输。结合研究表明，LEU-114是BNIP1的pro凋亡BH3结构域中高度组成的居住，对于与α-SNAP的相互作用至关重要，但与RINT-1相互作用至关重要。 α-SNAP的过表达明显延迟星形孢菌素诱导的细胞凋亡。这些结果提出了BNIP1在膜融合和凋亡之间的串扰中起作用的可能性。