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Membrane-Transport Signaling Involving the GTPase Cycle of G proteins

涉及 G 蛋白 GTP 酶循环的膜运输信号转导

基本信息

批准号：
18207008
负责人：
KATADA Toshiaki
金额：
$ 31.87万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-18207008/
关键词：
Signal transduction Protein Gene Genome project G protein GTPase cycle

项目摘要

G proteins, which cycle between the two different conformations of GTP- and GDP-bound states, play important roles as a "molecular switch" in many intracellular signaling pathways. The G protein families include 1) translation factors involved in protein synthesis and mRNA degradation, 2) trimeric G proteins, and 3) small GTPases. The small GTPases, such as Ras, Rab, Arf, and Rho/Rac family, are involved in the regulation of cell growth and differentiation, intracellular vesicle trafficking, and cell shape and adhesion. However, there are still many other small GTPases, of which functions are unknown. In this study, we have identified and characterized novel small GTPases exhibiting unique biochemical properties or tissue expression.1. The Arl8 GTPase was essential for lysosome biogenesis in the macrophage-like coelomocytes of C. elegans: ARL-8 localized primarily to lysosomes, and a deletion mutant of arl-8 displayed an increase in number of lysosomes that were small in size and non-a … More cidic. Extracellular macromolecules were endocytosed and transported through endosomes in arl-8 mutant coelomocytes, but its degradation was markedly reduced. Thus, Arl8 appeared to function as an important regulator of lysosome biogenesis/function.2. Rab45 is an atypical GTPase that contains a coiled-coil motif at the mid region and a distinct N-terminal EF-hand domain with C-terminal Rab-homology domain. Rab45 was capable of self-interacting, and the self-interaction required the mid region containing the coiled-coil motif. Rab45 expressed in HeLa cells was localized in a small patch in the perinuclear area of the cell, and the localization was regulated by the guanine nucleotide-bound states of Rab45. The mid region, together with Rab domain, appeared to be essential for the characteristic perinuclear localization of Rab45.3. Di-Ras, which belongs to a distinct branch of the Ras family, existed predominantly as a GTP-bound form in living cells. The expression of Di-Ras was rather specific in neuronal cells, and its over-expression induced apoptotic cell death with DNA fragmentation in neuronal cells. A deletion mutant of arl-8 in C. elegans displayed a phenotype that acetylcholine release from nerve cells might be impaired. Less

G蛋白在GTP和GDP两种不同的结合状态之间循环，在许多细胞内信号传导途径中作为“分子开关”发挥重要作用。G蛋白家族包括1）参与蛋白质合成和mRNA降解的翻译因子，2）三聚体G蛋白，和3）小GTP酶。Ras、Rab、Arf和Rho/Rac家族等小分子GTP酶参与调节细胞的生长和分化、胞内囊泡的运输以及细胞的形状和粘附。然而，还有许多其他的小GTP酶，其功能是未知的。在这项研究中，我们已经确定并表征了新的小GTP酶，其表现出独特的生物化学特性或组织表达。Ar 18 GTdR是巨噬细胞样体腔细胞中溶酶体生物合成所必需的。优雅：ARL-8主要定位于溶酶体，而arl-8的缺失突变体表现出溶酶体数量的增加，这些溶酶体体积小，不含蛋白质。 ...更多信息 cidic。在arl-8突变体体腔细胞中，细胞外大分子被内吞并通过内体转运，但其降解明显减少。因此，Ar 18似乎作为溶酶体生物发生/功能的重要调节剂起作用。Rab 45是一种非典型的GTdR，其在中间区域含有卷曲螺旋基序，并且在C-末端含有Rab-homologous结构域。Rab 45具有自我相互作用的能力，而自我相互作用需要含有卷曲螺旋基序的中间区域。Rab 45在HeLa细胞中的表达定位于细胞核周区的小块区域中，并且该定位受Rab 45的鸟嘌呤核苷酸结合状态的调节。中间区域，连同Rab结构域，似乎是必不可少的特征Rab45.3的核周定位。Di-Ras属于Ras家族的一个独特分支，主要以GTP结合形式存在于活细胞中。Di-Ras在神经细胞中的表达具有特异性，其过表达可诱导神经细胞凋亡并伴有DNA片段化。在C.线虫表现出神经细胞乙酰胆碱释放受损的表型。少