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2013诺贝尔生理学或医学奖揭晓：詹姆斯·E·罗斯曼（James E. Rothman）兰迪·谢克曼（Randy W. Schekman) 托马斯·聚德霍夫（Thomas C. Südhof)
2013诺贝尔生理学或医学奖授予授予詹姆斯·罗斯曼，兰迪·谢克曼以及托马斯·聚德霍夫，以表彰他们对对于细胞内物质运输机制的研究贡献。
2013年诺贝尔生理学或医学奖授予了三位解开细胞如何组织其运输系统之谜的科学家。每个细胞如同一座工厂，制造和输出着各类分子比如胰岛素产生后释放到血液中，而被称为神经传递素的化学信号则通过一个神经细胞传递到另外一个神经细胞。这些分子都被运输到细胞周围的被称为囊泡的小“包裹”中。这次获奖的三位科学家解开了调控运输物在正确时间投递到细胞中正确位置的分子原理。
Randy Schekman发现了囊泡传输所需的一组基因；James Rothman阐明了囊泡是如何与目标融合并传递的蛋白质机器；Thomas Südhof则揭示了信号是如何引导囊泡精确释放被运输物的。
通过研究，Rothman, Schekman和Südhof揭开了细胞物质运输和投递的精确控制系统的面纱。该系统的失调会带来有害影响，并可导致诸如神经学疾病、糖尿病和免疫学疾病等的发生。
物质是如何传递到细胞内
对于一个庞大且繁忙的港口，需要一套运行体制保证正确的货物在正确的时间运送到正确的地点。细胞，有着被称为细胞器的不同“隔间”，也面临着类似问题：细胞产生分子物质如荷尔蒙、神经传递素、细胞因子、酶等，然后将这些物质在正确的时间里传送到细胞中其他地方或者细胞外。时间和地点决定一切。囊泡体积微小、呈泡状，外面包裹着膜，或在细胞器之间来回运输物质、或与细胞外膜融合将物质释放在外。这一过程十分重要，因为该过程可在有递质的条件下触发神经活动，或在有荷尔蒙的条件下控制代谢。囊泡又如何知道何时何地“发货”呢？
“交通堵塞”揭示遗传控制
Randy Schekman醉心于研究细胞如何组织其运输系统，他在上个世纪70年代决定利用酵母菌作为模型系统来从遗传原理上研究该系统。通过遗传筛查，他发现酵母菌的运输机制有缺陷，其运输系统很差劲，囊泡在细胞的特定区域堆积。他发现导致这种“堵塞”的原因是遗传的，便继续研究，试图找到变异的基因。Schekman发现三类基因能够控制细胞运输系统的不同方面，从而为了解细胞囊泡运输的精密调控机制提供一种新认识。
精确“停靠”
James Rothman同样着迷于研究细胞运输系统的本质。当Rothman在上个世纪80至90年代研究哺乳动物细胞内的囊泡运输时，他发现一种蛋白复合物能让囊泡进入并融合目标膜。在融合过程中，囊泡上的蛋白质与目标膜如同拉链一般相互结合。这样的蛋白质数量很多且只以特定方式结合，如此使得运输物质能够投递到精确位置。同样的原理也在细胞内运行着，当囊泡与细胞外膜结合时便释放其内容物。
后来人们发现，Schekman在酵母菌中发现的基因一部分可编码Rothman在哺乳动物中找到的那些蛋白，从而揭开了这种运输系统的古老进化起源。他们一同绘制出了这种细胞运输机制的关键部分。
时机就是一切
Thomas Südhof对于脑中的神经细胞如何相互交流很感兴趣。信号分子——神经递质从囊泡中释放，通过Rothman和Schekman发现的机制，与神经细胞的外膜融合。不过，只有当神经细胞向其“邻居”发信号时，这些囊泡才被“允许”释放其内容物。这种控制方式为何如此精确？已知的是，钙离子参与其中，在1990年代，Südhof在神经细胞中搜索钙敏感蛋白。他鉴别出这种分子机制，即响应钙离子流入，指导临近蛋白快速将囊泡绑定至神经细胞外膜。“拉链”开启，信号物质释放出来。Südhof的发现解释了短暂的精确如何实现，以及囊泡内容物如何按指令释放。
囊泡运输有助理解疾病过程
三位诺奖得主发现了细胞生理学的一个基础性过程。这些发现对于我们理解“货物”如何以完美的时机和精确性在细胞内外进行转运具有重大的影响。在从酵母到人类的众多有机体中，囊泡运输和融合采用的是相同的原理。这一系统对于众多的生理学过程极为重要，在这些生理学过程中，囊泡融合必须被控制，包括在脑中发信号以及释放荷尔蒙和免疫因子。缺陷性囊泡运输发生于许多疾病中，包括大量神经性和免疫性疾病，以及糖尿病。若是没有这一奇妙的精确组织，细胞将会堕入混乱的深渊。
The Nobel Prize in Physiology or Medicine 2013 was awarded jointly to James E. Rothman, Randy W. Schekman and Thomas C. Südhof "for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells".
詹姆斯·E·罗斯曼（James E. Rothman），耶鲁大学细胞生物学系系主任、纪念Fergus F. Wallace生物医学教授。他曾获得多种荣誉，包括哥伦比亚大学的露依莎·格罗斯·霍维茨奖、拉斯克奖基础医学奖（2002年）、费萨尔国王奖。他在耶鲁大学取得硕士学位，在哈佛获博士学位。获2013年诺贝尔生理学或医学奖.
兰迪·谢克曼（Randy W. Schekman，日－）是一位来自加州大学伯克利分校的细胞生物学家，曾任《美国国家科学院院刊》主编。[2][3][4] 1992年当选美国国家科学院院士。2002年与詹姆斯·罗思曼因对细胞膜传输的研究获拉斯克基础医学奖,获2013年诺贝尔生理学或医学奖 。
托马斯·聚德霍夫（Thomas C. Südhof，日生于德国哥廷根），德国生物化学家，以研究突触传递知名。自1986年以来聚德霍夫博士的研究已经阐明了许多主要的蛋白介导突触前功能。2013年，他和理查德·舍勒分享了拉斯克基础医学奖。获2013年诺贝尔生理学或医学奖 。
Press Release
The Nobel Assembly at Karolinska Institutet has today decided to award
The 2013 Nobel Prize in Physiology or Medicine
jointly to
James E. Rothman, Randy W. Schekman
and Thomas C. Südhof
for their discoveries of machinery regulating vesicle traffic,
a major transport system in our cells
The 2013 Nobel Prize honours three scientists who have solved the mystery of how the cell organizes its transport system. Each cell is a factory that produces and exports molecules. For instance, insulin is manufactured and released into the blood and chemical signals called neurotransmitters are sent from one nerve cell to another. These molecules are transported around the cell in small packages called vesicles. The three Nobel Laureates have discovered the molecular principles that govern how this cargo is delivered to the right place at the right time in the cell.
Randy Schekman discovered a set of genes that were required for vesicle traffic. James Rothman unravelled protein machinery that allows vesicles to fuse with their targets to permit transfer of cargo. Thomas Südhof revealed how signals instruct vesicles to release their cargo with precision.
Through their discoveries, Rothman, Schekman and Südhof have revealed the exquisitely precise control system for the transport and delivery of cellular cargo. Disturbances in this system have deleterious effects and contribute to conditions such as neurological diseases, diabetes, and immunological disorders.
How cargo is transported in the cell
In a large and busy port, systems are required to ensure that the correct cargo is shipped to the correct destination at the right time. The cell, with its different compartments called organelles, faces a similar problem: cells produce molecules such as hormones, neurotransmitters, cytokines and enzymes that have to be delivered to other places inside the cell, or exported out of the cell, at exactly the right moment. Timing and location are everything. Miniature bubble-like vesicles, surrounded by membranes, shuttle the cargo between organelles or fuse with the outer membrane of the cell and release their cargo to the outside. This is of major importance, as it triggers nerve activation in the case of transmitter substances, or controls metabolism in the case of hormones. How do these vesicles know where and when to deliver their cargo?
Traffic congestion reveals genetic controllers
Randy Schekman was fascinated by how the cell organizes its transport system and in the 1970s decided to study its genetic basis by using yeast as a model system. In a genetic screen, he identified yeast cells with defective transport machinery, giving rise to a situation resembling a poorly planned public transport system. Vesicles piled up in certain parts of the cell. He found that the cause of this congestion was genetic and went on to identify the mutated genes. Schekman identified three classes of genes that control different facets of the cell?s transport system, thereby providing new insights into the tightly regulated machinery that mediates vesicle transport in the cell.
Docking with precision
James Rothman was also intrigued by the nature of the cell?s transport system. When studying vesicle transport in mammalian cells in the 1980s and 1990s, Rothman discovered that a protein complex enables vesicles to dock and fuse with their target membranes. In the fusion process, proteins on the vesicles and target membranes bind to each other like the two sides of a zipper. The fact that there are many such proteins and that they bind only in specific combinations ensures that cargo is delivered to a precise location. The same principle operates inside the cell and when a vesicle binds to the cell?s outer membrane to release its contents.
It turned out that some of the genes Schekman had discovered in yeast coded for proteins corresponding to those Rothman identified in mammals, revealing an ancient evolutionary origin of the transport system. Collectively, they mapped critical components of the cell?s transport machinery.
Timing is everything
Thomas Südhof was interested in how nerve cells communicate with one another in the brain. The signalling molecules, neurotransmitters, are released from vesicles that fuse with the outer membrane of nerve cells by using the machinery discovered by Rothman and Schekman. But these vesicles are only allowed to release their contents when the nerve cell signals to its neighbours. How is this release controlled in such a precise manner? Calcium ions were known to be involved in this process and in the 1990s, Südhof searched for calcium sensitive proteins in nerve cells. He identified molecular machinery that responds to an influx of calcium ions and directs neighbour proteins rapidly to bind vesicles to the outer membrane of the nerve cell. The zipper opens up and signal substances are released. Südhof?s discovery explained how temporal precision is achieved and how vesicles? contents can be released on command.
Vesicle transport gives insight into disease processes
The three Nobel Laureates have discovered a fundamental process in cell physiology. These discoveries have had a major impact on our understanding of how cargo is delivered with timing and precision within and outside the cell. Vesicle transport and fusion operate, with the same general principles, in organisms as different as yeast and man. The system is critical for a variety of physiological processes in which vesicle fusion must be controlled, ranging from signalling in the brain to release of hormones and immune cytokines. Defective vesicle transport occurs in a variety of diseases including a number of neurological and immunological disorders, as well as in diabetes. Without this wonderfully precise organization, the cell would lapse into chaos.
James E. Rothman was born 1950 in Haverhill, Massachusetts, USA. He received his PhD from Harvard Medical School in 1976, was a postdoctoral fellow at Massachusetts Institute of Technology, and moved in 1978 to Stanford University in California, where he started his research on the vesicles of the cell. Rothman has also worked at Princeton University, Memorial Sloan-Kettering Cancer Institute and Columbia University. In 2008, he joined the faculty of Yale University in New Haven, Connecticut, USA, where he is currently Professor and Chairman in the Department of Cell Biology.
Randy W. Schekman was born 1948 in St Paul, Minnesota, USA, studied at the University of California in Los Angeles and at Stanford University, where he obtained his PhD in 1974 under the supervision of Arthur Kornberg (Nobel Prize 1959) and in the same department that Rothman joined a few years later. In 1976, Schekman joined the faculty of the University of California at Berkeley, where he is currently Professor in the Department of Molecular and Cell biology. Schekman is also an investigator of Howard Hughes Medical Institute.
Thomas C. Südhof was born in 1955 in G?ttingen, Germany. He studied at the Georg-August-Universit?t in G?ttingen, where he received an MD in 1982 and a Doctorate in neurochemistry the same year. In 1983, he moved to the University of Texas Southwestern Medical Center in Dallas, Texas, USA, as a postdoctoral fellow with Michael Brown and Joseph Goldstein (who shared the 1985 Nobel Prize in Physiology or Medicine). Südhof became an investigator of Howard Hughes Medical Institute in 1991 and was appointed Professor of Molecular and Cellular Physiology at Stanford University in 2008.
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