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BIODYNAMICS OF NUCLEAR MEMBRANE AND MATRIX

核膜和基质的生物动力学

基本信息

批准号：
3277772
负责人：
MELVIN S SCHINDLER
金额：
$ 4.5万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1982
资助国家：
美国
起止时间：
1982-01-01 至 1991-03-31
项目状态：
已结题

项目摘要

The observation of protein mobility on the outer membrane and immobility on the inner membrane of rat liver nuclei suggests that these membranes may in fact be two functionally different compartments. A dynamic outer membrane may be part of a diffusion pathway, important for nuclear glycoprotein biosynthesis and redistribution of mixed function monooxygenase components between endoplasmic reticulum (E.R.) and nuclear compartments. A non-dynamic inner nuclear membrane containing topologically restrained proteins suggests a role for this membrane in processes requiring organic protein structures and stable multi-enzyme complexes, e.g. - transcription, replication, mRNA translocation. Future experiments are designed to pursue these results by using lateral mobility as a probe for nuclear structure, and as a means to evaluate the validity of mechanisms explaining nuclear-intracellular communication. Antibodies to cytochrome P-450 and P-450 reductase, both outer nuclear membrane proteins, provide specific markers for evaluating the role of outer membrane as a two dimensional communication pathway between cell compartments. Investigations of inner nuclear membrane will seek to explore the role of membrane associated structures, e.g. lamins, chromatin, and ribonucleoproteins in anchoring inner membrane proteins. Substances capable of specifically altering each membrane associated component, e.g. DNAase I, micrococcal nuclease, RNAase, proteases, salts, will be examined with regard to effects on lateral mobility. Another aspect of nuclear diffusion to be investigated will be trans-nuclear membrane transport mediated by the nuclear pore complex. Rates of nucleocytoplasmic transport for model dextran compounds and nuclear and non-nuclear proteins of equivalent size will be compared. These investigations may help define energetic requirements and protein three dimensional structure or sequence that enhance transmembrane transport. A new biochemical perspective on nuclear-intracellular communication is now possible because of the observation that nuclear glycoproteins contain a unique oligosaccharide moiety. Using this as a marker it will be possible to explore whether nuclear membrane and cytoskeletal glycoproteins are synthesized at the nucleus or follow the more conventional endoplasmic reticulum-Golgi pathways. It is hoped that these diverse approaches will provide significant new information relating various aspects of nuclear structure to mechanisms of nuclear-intracellular-plasma membrane communication.

蛋白质在外膜上的迁移率和在外膜上的固定性的观察大鼠肝细胞核的内膜提示这些膜可能在事实是两个功能不同的隔间。一种动态的外膜可能是扩散途径的一部分，对核糖蛋白很重要混合功能单加氧酶组分的生物合成和重分布内质网之间(E.R.)和核弹舱。一个包含拓扑约束的非动态内核膜蛋白质表明，这种膜在需要有机物质的过程中发挥了作用蛋白质结构和稳定的多酶复合体，例如转录，复制，信使核糖核酸易位。未来的实验旨在进行这些结果是通过使用横向迁移率作为核结构的探针，作为评估机制解释有效性的一种手段细胞核与细胞内的通讯。细胞色素P-450抗体和 P-450还原酶，这两种外核膜蛋白，提供了特定的评价外膜作为二维膜的作用的标志物细胞间隔室之间的通讯途径。对内部的调查核膜将寻求探讨膜相关的作用锚定中的结构，如层粘连蛋白、染色质和核糖核蛋白内膜蛋白。能够特别改变每一种物质膜相关成分，如DNAase I，微球菌核酸酶，RNA酶，将检查蛋白水解酶、盐对侧向的影响。机动性。要调查的核扩散的另一个方面是核孔复合体介导的跨核膜转运。模型葡聚糖化合物的核质转运速率和我们将比较同等大小的核蛋白和非核蛋白。这些研究可能有助于确定能量需求和蛋白质增强跨膜的三维结构或序列运输。细胞内核生化研究的新视角通信现在是可能的，因为观察到核能糖蛋白含有一种独特的寡糖部分。将其用作标记物将有可能探索核膜和核膜细胞骨架糖蛋白是在细胞核中合成的，或者跟随更传统的内质网-高尔基体途径。人们希望，这些不同的方法将提供重要的新信息，从核结构的各个方面到核反应的机制核-胞内-质膜通讯。