2003 Fiscal Year Final Research Report Summary
Cross-talk between membrane fusion, cell cycle, and apoptosis
| Project/Area Number |
14380339
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
TAGAYA Mitsuo Tokyo University of Pharmacy and Life Science, School of Life Science, Professor, 生命科学部, 教授 (30179569)
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| Co-Investigator(Kenkyū-buntansha) |
HATSUZAWA Kiyotaka Fukushima Medical University, School of Medicine, lecturer, 医学部, 講師 (20256655)
NAGAHAMA Masami Tokyo University of Pharmacy and Life Science, School of Life Science, Research Associate, 生命科学部, 助手 (60281169)
TANI Katsuko Tokyo University of Pharmacy and Life Science, School of Life Science, Associate Professor, 生命科学部, 助教授 (40266896)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Endoplasmic reticulum / Membrane fusion / Vesicular transport / Cell cycle / Apoptosis |
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| Research Abstract |
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 complex
Two-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 Golgi
Overexpression, 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 fusion
BNIP1 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.
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Research Products
(11 results)
