Mode of actions and functions of the Rab3A and SNARE systems in neurotransmitter release
Rab3A 和 SNARE 系统在神经递质释放中的作用模式和功能
基本信息
- 批准号:11670118
- 负责人:
- 金额:$ 2.3万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:1999
- 资助国家:日本
- 起止时间:1999 至 2000
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
It has been revealed that the Rab3A, a small GTPase, and SNARE systems are involved in neurotransmitter release. The Rab3A system consists of its target protein, which interacts with the GTP-bound form of Rab3A but not with the GDP-bound form of Rab3A, and its several regulatory proteins. We have identified Rabphilin-3 as a target protein for Rab3A and revealed the possibility that Rabphilin-3 functions as a Ca^<2+>-sensor in the presynapse. On the other hand, available evidence suggests that the SNARE system functions at the downstream of the Rab3A system and is implicated in neurotransmitter release. We have identified Tomosyn as a regulatory protein of the SNARE system. It is possible that Tomosyn is a central player which links between the Rab3A and SNARE systems. However, the mechanism by which the Rab3A system regulates the SNARE system in neurotransmitter release remains to be clarified. Therefore, in this study we attempted to clarify the mechanism. We revealed that there were at least three isoforms of Tomosyn, b-, m-, and s-Tomosyns and that all of the tomosyn isoforms interacted through their C-terminal VAMP-like regions with syntaxin-1 but not with other syntaxin isoforms such as syntaxin-2, -3, and -4. Moreover, we identified a novel syntaxin-1-binding protein. On the basis of its biochemical properties, it was possible that the syntaxin-1-binding protein was a cytoskeleton-related protein. One mole of the syntaxin-1-binding protein bound to about 0.8 mole of syntaxin-1 and the dose giving the half maximal binding of syntaxin-1 to the syntaxin-1-binding protein was about 90 nM.The interaction of the syntaxin-1-binding protein with syntaxin-1 was inhibited by Munc18 in a dose-dependent manner. In future we attempt to purify the syntaxin-1-binding protein, determine its primary structure, and reveal its function in neurotransmitter release.
研究表明,Rab3A是一个小的GTP酶,SNARE系统参与了神经递质的释放。Rab3A系统由其靶蛋白和几个调节蛋白组成,后者与GTP结合的Rab3A相互作用,而不与GDP结合的Rab3A相互作用。我们已经确定RabPhilin-3是Rab3A的靶蛋白,并揭示了RabPhilin-3在突触前中作为钙离子感受器发挥作用的可能性。另一方面,现有证据表明,SNARE系统在Rab3A系统下游发挥作用,并与神经递质释放有关。我们已经确定Tomosyn是SNARE系统的一种调节蛋白。Tomosyn可能是连接Rab3A和SNARE系统的中心参与者。然而,Rab3A系统调节SNARE系统神经递质释放的机制尚不清楚。因此,在本研究中,我们试图阐明其机制。我们揭示了Tomosyns至少存在三种亚型,即b-、m-和S-Tomosynns,并且所有的Tomosyn亚型都通过其C端的VAMP样区与Synaxin-1相互作用,而不与其他Synaxin-2、-3和-4亚型相互作用。此外,我们还鉴定了一个新的Synaxin-1结合蛋白。根据其生化特性,推测该蛋白可能是一种细胞骨架相关蛋白。1摩尔的合成素-1结合蛋白与约0.8摩尔的合成素-1结合,使合成素-1与合成素-1结合一半的剂量约为90 nm。Munc18以剂量依赖的方式抑制合成素-1结合蛋白与合成素-1的相互作用。在未来,我们试图纯化合成素-1结合蛋白,确定其一级结构,并揭示其在神经递质释放中的功能。
项目成果
期刊论文数量(11)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
shirataki,H.,Sasaki,T.,and Takai,Y.: "Rabphilin-3 : a target molecule for Rab3 small G proteins."Methods in Enzymology. 329巻. 75-82 (2001)
shirataki, H.、Sasaki, T. 和 Takai, Y.:“Rabphilin-3:Rab3 小 G 蛋白的靶分子。”酶学方法 329. 75-82 (2001)。
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Yokoyama,S.,Shirataki,H.,Sakisaka,T.,and Takai,Y.: "Three splicing variants of Tomosyn and identification of their syntaxin-binding region."Biochem.Biophys.Res.Commun.. 256巻1号. 218-222 (1999)
Yokoyama, S.、Shirataki, H.、Sakisaka, T. 和 Takai, Y.:“Tomosyn 的三种剪接变体及其突触蛋白结合区域的鉴定。”Biochem.Biophys.Res.Commun.。第 256 卷,第 1 号 218-222 (1999)
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Kobayashi, N., Higashi, T., Hara, K., Shirataki, H., and Matsuoka, H.: "Effects of imidapril on NOS expression and myocardial remodelling in failing heart of Dahl salt-sensitive hyper - tensive rats."Cardiovasc. Res.. 44. 518-526 (1999)
Kobayashi, N.、Higashi, T.、Hara, K.、Shirataki, H. 和 Matsuoka, H.:“咪达普利对 Dahl 盐敏感性高血压大鼠衰竭心脏中 NOS 表达和心肌重塑的影响”。
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Kobayashi,N.,Higashi,T.,Hara,K.,Shirataki,H.,and Matsuoka,H.: "Effects of imidapril on NOS expression and myocardial remodelling in failing heart of Dahl salt-senditive hypertensive rats"Cardiovasc.Res.. 44巻3号. 518-526 (1999)
Kobayashi, N.、Higashi, T.、Hara, K.、Shirataki, H. 和 Matsuoka, H.:“咪达普利对 Dahl 盐敏感性高血压大鼠衰竭心脏中 NOS 表达和心肌重塑的影响”Cardiovasc.Res ..第 44 卷第 3 期。518-526 (1999)
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Higashi, T., Kobayashi, N., Hara, K., Shirataki, H., and Matsuoka, H.: "Effects of angiotensin II type I receptor antagonist on nitric oxide synthase expression and myocardial remodelling in Goldblatt hypertensive rats."J.Cardiovasc.Pharm.. 35. 564-571 (2
Higashi, T.、Kobayashi, N.、Hara, K.、Shirataki, H. 和 Matsuoka, H.:“血管紧张素 II I 型受体拮抗剂对 Goldblatt 高血压大鼠一氧化氮合酶表达和心肌重塑的影响。”J
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SHIRATAKI Hiromichi其他文献
SHIRATAKI Hiromichi的其他文献
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{{ truncateString('SHIRATAKI Hiromichi', 18)}}的其他基金
Role and function of taxilin in the complex formation of molecules related to intracellular signal transduction in a regenerating liver
紫杉素在再生肝脏细胞内信号转导相关分子复杂形成中的作用和功能
- 批准号:
23659403 - 财政年份:2011
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Analysis of taxilin-dependent co-operative regulation of the rearrangement of the microtubule cytoskeleton and intracellular vesicle transport
紫杉素依赖性协同调节微管细胞骨架重排和细胞内囊泡运输的分析
- 批准号:
19590285 - 财政年份:2007
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Roles and mode of action of Taxilin family in invasion and metastasis of malignant cells
Taxilin家族在恶性肿瘤细胞侵袭转移中的作用及作用方式
- 批准号:
17590276 - 财政年份:2005
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Formation of microdomains of the plasma membrane that are involved in intracellular signal transduction
参与细胞内信号转导的质膜微结构域的形成
- 批准号:
13670130 - 财政年份:2001
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Function and action of Rab3A in neurotransmitter release
Rab3A 在神经递质释放中的功能和作用
- 批准号:
09670126 - 财政年份:1997
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)














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