08 October 2013

Nobel Bubbles

"Bubble transport" in living cells

Maxim Russo, <url>

The 2013 Nobel Prize in Physiology and Medicine was awarded to three scientists who became famous for their research in the field of cell biology. James E. Rothman is the head of the Department of Cell Biology at Yale University School of Medicine, Randy W. Sheckman. Schekman) works at the University of California, Berkeley. Thomas Sudhof, a native of Germany, has been working in the USA since 1983, now he is a professor of molecular and cellular physiology at Stanford University. They were able to establish how the mechanism of transport of molecules through cell membranes works.

From left to right: James Rothman, Thomas Sudhof, Randy Sheckman

The secretary of the Nobel Committee for Physiology and Medicine, which traditionally has to announce the laureates in all languages that Alfred Nobel spoke, speaking in Russian, mentioned "bubble transport". In fact, in Russian scientific terminology there has long been a concept – vesicular mechanism, or vesicular transport.

For the normal life of an organism, its cells must be able to receive and send molecules of various substances, for example, hormones. But the molecules of these substances are not able to overcome the cell membrane. In order for the transport of substances between cells to function normally, there are vesicles – small bubbles (Latin vesicula "bubble") surrounding the molecules of these substances with a thin membrane. The vesicle membrane is similar to the membrane that surrounds the cell. When a cell "needs" to release some substance into the external environment, a vesicle containing a molecule of this substance moves to the cell membrane and merges with it, and its contents are ejected into the extracellular space. A cell can also capture a molecule from its surface, in which case the cell membrane forms a depression, surrounds the molecule associated with receptors on the cell surface, and eventually closes over it. A molecule surrounded by a membrane layer breaks away from the outer membrane, and an intracellular vesicle is formed.

Similar things happen inside the cell. Individual cell organelles are surrounded by membranes, and communication between them is possible by transferring molecules through vesicles. For example, it is the vesicles that deliver proteins from the endoplasmic reticulum to the Golgi apparatus. The destruction of proteins that have fulfilled their function in the cell is also not complete without the participation of vesicles. A special protein ubiquitin is attached to the protein molecule inside the cell, a vesicle appears around the molecule, which delivers it to a special organ of the cell – the proteasome, where the protein is destroyed.

Randy Sheckman, in experiments with yeast cells (Saccharomyces cerevisiae), established 23 genes that encode proteins responsible for the functioning of vesicular transport. James Rothman studied proteins in cellular structures that ensure the formation and movement of vesicles. The first protein he isolated was N-ethylmaleimide-sensitive factor (NSF). The discovery of the first protein was soon followed by a sequel. At the moment, several dozen proteins are known that are involved in the fusion of vesicles with the membrane. Thomas Sudhof investigated the mechanism of vesicular transport in synapses, contacts between nerve cells, where vesicles contain a neurotransmitter – a substance that provides the transmission of a nerve impulse. Sudhof found that the process of releasing a neurotransmitter from vesicles is triggered by an increase in the content of calcium ions in the cytoplasm.

Understanding how the movement of substances in the cells of the body is organized is of great importance for medicine. A number of diseases are associated with disorders of "intercellular transport". Some types of epilepsy are associated with a mutation in the gene encoding the MUNC-18-1 protein, which is involved in the vesicular mechanism in synapses. In such a disease as familial hemophagocytic lymphohistiocytosis, due to mutations of genes encoding vesicular transport proteins, natural killer lymphocytes cannot respond properly to target cells, which ultimately leads to death. In botulism, the toxin of the bacterium Clostridium botulinum destroys the SNAP25 protein, which ensures the formation of vesicles with a neurotransmitter, and this is what blocks the transmission of nerve impulses and causes paralysis.

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The award of the Nobel Prize in Physiology and Medicine was commented for Polit.Elena Nadezhdina, Doctor of Biological Sciences, Chief Researcher, Head of the Cell Biology Group of the Protein Institute of the Russian Academy of Sciences, Deputy. Head of the Department of Functional Biochemistry of Biopolymers of the Research Institute of Physico-Chemical Biology named after A.N. Belozersky Moscow State University. Natalia Demina was talking.

– Were the names of the three Nobel Prize winners in Physiology a surprise to you?

– These are quite well–known scientists in their field, for their good work they received a well-deserved award in the way in which it has been given in recent years.

– How would you describe the principle of the selection of laureates by the Nobel Committee in recent years?

– These should be solid scientists who have made a significant contribution. They should be well known to the scientific community.

– According to the reaction of journalists at the press conference at the Nobel Committee, it seemed that these three names were completely unexpected…

– Yes, it was unexpected, because there were other assumptions on more applied research – cancer therapy and others. But the winners are really the ones who deserve the prize. Their names are in textbooks, their contribution is fundamental, but somehow everyone forgot about them…

– Why is their research important?

– Their work is related to the knowledge of the fundamental foundations of a living cell. Vesicular transport was the part of intracellular biology that was least studied a few decades ago. They took it up and were able to understand the mechanism of its work. Naturally, they are not the only ones, many other researchers have worked in this field. But these three really made a significant contribution. And now a lot has become clear to us about how vesicular transport works.

– Are you familiar with any of the laureates, could you share your personal impressions?

– No, I don't know anyone. Unfortunately, almost no one in Russia deals with this section. Except for a small group at the Institute of Cytology of the Russian Academy of Sciences in St. Petersburg. We started doing this ourselves only some time ago, however, we were concerned about several other aspects of the problem.

– Why is this area not being studied in Russia? What is the reason?

– Historically, this was not done until the mid-80s, but when they began to do it more intensively in the West, there was no longer enough funding in Russia. In science, starting a new topic is always more expensive than continuing an already known field.

– To what extent do the Nobel Prizes encourage young scientists to work in science?

– It seems to me that this award is most important for the PR of science. Somehow it so happened that the society of people who are not engaged in science takes these awards seriously, almost everyone knows what it is. These awards have managed to maintain their status, and it is believed that they are given for outstanding discoveries. A scientist cannot be guided in his activity by the principle "Should I get a Nobel Prize?". There are many more local awards in any countries and any branches of science, but normal scientists do not work to receive awards. If someone has such ambitious plans, they arise at later stages of a scientific career, when a person reaches a certain position.

Portal "Eternal youth" http://vechnayamolodost.ru08.10.2013

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