How Single Genes Provide Proteins to Multiple Cellular Compartments; Collaborative Research
单基因如何向多个细胞区室提供蛋白质;
基本信息
- 批准号:9506810
- 负责人:
- 金额:$ 40.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:1995
- 资助国家:美国
- 起止时间:1995-09-01 至 2001-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
9506810 Hopper and Martin The Hopper and Martin laboratories collaboratively study an unusual category of yeast genes that code for "sorting isozymes". These are enzymes coded by the same gene but located in more than one subcellular compartment. Study of these genes has provided information about the cis signals that target proteins to their correct destination, and promises to provide a means of uncovering gene products that play roles in the sorting process. TRM1 codes for 2 isozymes, an amino-terminal extended protein found in mitochondria and a protein lacking the extension found in mitochondria and nuclei, MOD5 also encodes 2 isozymes; the amino-terminal extended Mod5p is in mitochondria and the form lacking this extension is in nuclei, but the cytosol has contributions from both isozymes. CCA1 codes for 3 isozymes. The amino-terminal extended longest form is located in mitochondria and the other two forms are in cytosol/nuclear compartments. Trm1p, Mod5p, and Cca1p are all involved in tRNA biosynthesis. tRNAs encoded by the nuclear genome are located in the cytosol and the nucleus. One goal of the proposed studies is to determine whether cells require both nuclear and cytoplasmic forms of Mod5p and Cca1p for the reactions they carry out. In addressing this problem, sequences necessary and sufficient for nuclear import of these proteins will be identified. Then the sequences will be altered to determine the consequences of mislocalizing them. The amino-extended forms of Trm1p and probably Cca1 and Mod5p possess both mitochondrial and nuclear targeting information, yet are not found in the nucleus. Mechanisms that could account for the dominance of the mitochondrial targeting information will be explored. In particular, the hypotheses that mitochondrial targeting signals play a role in coupling import to translation will be tested. These studies are timely as new information suggests an association of translation and mitochondrial protein i mport. Proper function of a eukaryotic cell is dependent upon appropriate subcellular distribution of proteins. Although there is a growing body of literature that addresses the trans-acting components that assure appropriate distribution, much remains to be learned. The hypothesis of the PI's is that the natural distribution of sorting isozymes to multiple cellular compartments can be used as a powerful new tool to study protein delivery to mitochondria and nuclei and that the outcome of such studies may have general applicability for understanding the sorting of proteins with a single subcellular destination as well as those with multiple destinations. The understanding of sequences necessary for the distribution of sorting isozymes allowed the PI's to devise genetic studies to identify components that affect the distribution process. The first genetic studies using Mod5p identified 4 genes: MDP1/RSP5, MDP2/VRP1, MDP4, and PAN1. Mutations of MDP2/VRP1 and PAN1 cause a decrease in the mitochondrial pool of Mod5p. Other mitochondrial proteins also may be affected because these mutations cause respiratory deficiency and conditional growth even though Mod5p itself is unessential. MDP2/ affects the actin cytoskeleton and PAN1 codes for a protein that interacts with 3' ends of mRNA and affects initiation of protein synthesis. Finding MDP2 and PAN1 implicates the actin cytoskeleton, proteins synthesis and 3' mRNA sequences in the distribution of proteins between the mitochondrial and the cytoplasm. Studies to decipher the mechanism of action of MDP2 and PAN1 are proposed. Success using one sorting isozyme to identify genes that alter its distribution to mitochondria predicts success of complementary studies to identify additional genes that alter the distribution of Mod5p as well as Cca1p. Genetic schemes to accomplish this are described in the proposed work. %%% This is a project engaged by two collaborating women scientists, one a biochemist and one a geneticist, who use multidisciplinary approaches to a fundamental question in biotechnology: how a protein which is the product of a single gene can be sorted to multiple locations within the cell. The basic problem behind cellular protein traffic is how to coordinate that protein traffic in the context of a structurally complex cytoplasm, composed of many different membrane-bound and non-membrane delimited compartments. If a protein is targeted to a single compartment, it can be initially made with a "targeting signal" which can subsequently be cleaved, depending on whether it is necessary for the protein's subsequent function. Targeting signals for the mitochondria and nucleus are known for several proteins which come to reside solely in those compartments, but this project concerns some proteins which are involved in tRNA modification which are found in both the mitochondria and nucleus and which contain both types of signals. The project examines what happens when these signals are changed in a way which changes the balance of the protein between the mitochondria and nucleus. Although the protein is coded by a single gene, different sizes of the protein exist, with the longer form found in mitochondria and the shorter form in the nucleus. Genetic analysis has found some intriguing genes which alter the amount of the longer form in the mitochondria. One of them affects the initiation of protein synthesis and one affects the actin cytoskeleton of the cell. The coupling of the synthesis (translation) of the protein to targeting to the mitochondria is examined. This project also addresses how altering the initiation of protein synthesis and the actin cytoskeleton can change the distribution of the protein between the nucleus and mitochondrion. This study provides insight into how the sorting information necessary for maintaining complex cellular compartmentation is regulated by the interactions of newly-made proteins with other cellular components. ***
9506810 霍珀和马丁 霍珀和马丁实验室合作研究一类不寻常的酵母基因,这些基因编码“分选同工酶”。 这些酶是由同一基因编码但位于多个亚细胞区室中的酶。 对这些基因的研究提供了有关将蛋白质靶向其正确目的地的顺式信号的信息,并有望提供一种发现在分选过程中发挥作用的基因产物的方法。 TRM1 编码 2 种同工酶,一种在线粒体中发现的氨基末端延伸蛋白,以及一种在线粒体和细胞核中发现的缺乏延伸的蛋白,MOD5 也编码 2 种同工酶;氨基末端延伸的 Mod5p 位于线粒体中,缺乏此延伸的形式位于细胞核中,但胞质溶胶有来自两种同工酶的贡献。 CCA1 编码 3 个同工酶。 氨基末端延伸的最长形式位于线粒体中,其他两种形式位于细胞质/核区室中。 Trm1p、Mod5p 和 Cca1p 均参与 tRNA 生物合成。 核基因组编码的 tRNA 位于细胞质和细胞核中。 拟议研究的目标之一是确定细胞进行的反应是否需要细胞核和细胞质形式的 Mod5p 和 Cca1p。 在解决这个问题时,将鉴定这些蛋白质向核输入所必需且充分的序列。 然后,这些序列将被改变,以确定它们错误定位的后果。 Trm1p 的氨基延伸形式以及可能的 Cca1 和 Mod5p 都具有线粒体和核靶向信息,但在细胞核中未发现。 将探索可以解释线粒体靶向信息的主导地位的机制。 特别是,线粒体靶向信号在输入与翻译耦合中发挥作用的假设将得到测试。 这些研究是及时的,因为新信息表明翻译与线粒体蛋白输入之间存在关联。 真核细胞的正常功能取决于蛋白质的适当的亚细胞分布。 尽管越来越多的文献探讨了确保适当分配的交易组件,但仍有许多东西有待学习。 PI 的假设是,分选同工酶在多个细胞区室中的自然分布可用作研究蛋白质向线粒体和细胞核递送的强大新工具,并且此类研究的结果可能具有普遍适用性,可用于理解具有单个亚细胞目的地以及具有多个目的地的蛋白质的分选。 了解分选同工酶分布所需的序列使 PI 能够设计遗传研究来识别影响分布过程的成分。 第一个使用 Mod5p 的遗传学研究确定了 4 个基因:MDP1/RSP5、MDP2/VRP1、MDP4 和 PAN1。 MDP2/VRP1 和 PAN1 的突变导致 Mod5p 线粒体库减少。 其他线粒体蛋白也可能受到影响,因为这些突变会导致呼吸缺陷和条件性生长,尽管 Mod5p 本身并不重要。 MDP2/ 影响肌动蛋白细胞骨架,PAN1 编码与 mRNA 3' 末端相互作用并影响蛋白质合成起始的蛋白质。 MDP2 和 PAN1 的发现暗示了肌动蛋白细胞骨架、蛋白质合成以及线粒体和细胞质之间蛋白质分布的 3' mRNA 序列。 提出了破译 MDP2 和 PAN1 作用机制的研究。 使用一种分选同工酶成功识别出改变其线粒体分布的基因预示着识别改变 Mod5p 和 Cca1p 分布的其他基因的补充研究的成功。 拟议的工作中描述了实现这一目标的遗传方案。 %%% 这是一个由两名合作的女科学家参与的项目,其中一名是生物化学家,另一名是遗传学家,她们使用多学科方法来解决生物技术中的一个基本问题:作为单个基因产物的蛋白质如何能够被分选到细胞内的多个位置。 细胞蛋白质运输背后的基本问题是如何在结构复杂的细胞质中协调蛋白质运输,细胞质由许多不同的膜结合和非膜分隔的区室组成。如果蛋白质被靶向单个区室,则最初可以用“靶向信号”来制备,随后可以将其切割,具体取决于该蛋白质的后续功能是否是必需的。 线粒体和细胞核的靶向信号因仅存在于这些区室中的几种蛋白质而闻名,但该项目涉及一些参与 tRNA 修饰的蛋白质,这些蛋白质同时存在于线粒体和细胞核中,并且包含两种类型的信号。该项目研究了当这些信号发生变化从而改变线粒体和细胞核之间的蛋白质平衡时会发生什么。 尽管该蛋白质是由单个基因编码的,但存在不同大小的蛋白质,较长的形式存在于线粒体中,较短的形式存在于细胞核中。 遗传分析发现了一些有趣的基因,它们可以改变线粒体中较长形式的数量。 其中一种影响蛋白质合成的起始,另一种影响细胞的肌动蛋白细胞骨架。 检查蛋白质合成(翻译)与靶向线粒体的耦合。该项目还探讨了如何改变蛋白质合成的起始和肌动蛋白细胞骨架来改变蛋白质在细胞核和线粒体之间的分布。 这项研究提供了关于维持复杂细胞区室所需的分选信息如何通过新制造的蛋白质与其他细胞成分的相互作用进行调节的见解。 ***
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Anita Hopper其他文献
Anita Hopper的其他文献
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{{ truncateString('Anita Hopper', 18)}}的其他基金
Collaborative Research: How Single Genes Provide Proteins to Multiple Cellular Compartments
合作研究:单基因如何向多个细胞区室提供蛋白质
- 批准号:
0115409 - 财政年份:2001
- 资助金额:
$ 40.85万 - 项目类别:
Continuing Grant
Macromolecular Instrumentation for Cell and Molecular Biology
细胞和分子生物学高分子仪器
- 批准号:
8804758 - 财政年份:1988
- 资助金额:
$ 40.85万 - 项目类别:
Standard Grant
Collaborative Research: Do Mitochondria Share Enzymes with the Rest of the Cell?
合作研究:线粒体与细胞其他部分共享酶吗?
- 批准号:
8601476 - 财政年份:1986
- 资助金额:
$ 40.85万 - 项目类别:
Continuing Grant
Do Mitochondria Share Enzymes with the Rest of the Cell? (Collaborative Research)
线粒体与细胞的其他部分共享酶吗?
- 批准号:
8302598 - 财政年份:1983
- 资助金额:
$ 40.85万 - 项目类别:
Continuing Grant
Control of Yeast Meiosis and Spore Formation By the Mating- Type Genes
交配型基因对酵母减数分裂和孢子形成的控制
- 批准号:
8009511 - 财政年份:1980
- 资助金额:
$ 40.85万 - 项目类别:
Standard Grant
Control of Yeast Meiosis and Spore Formation By the Mating-Type Genes
交配型基因对酵母减数分裂和孢子形成的控制
- 批准号:
7813643 - 财政年份:1978
- 资助金额:
$ 40.85万 - 项目类别:
Standard Grant
Control of Yeast Meiosis and Spore Formation By the Mating- Type Genes
交配型基因对酵母减数分裂和孢子形成的控制
- 批准号:
7600449 - 财政年份:1976
- 资助金额:
$ 40.85万 - 项目类别:
Standard Grant
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