Rewrite the textbook! To reveal a new mechanism of SNARE protein to assist intercellular and intercellular communication

Through Google search for "SNARE protein", Edward Chapman, a neuroscience professor at the University of Wisconsin Madison and a researcher at the Howard Hughes Medical Research Institute, obtained the structure diagram of a full screen spiral molecule When these proteins hold onto the outer membrane of two cells, they intertwine "Now, we have proven that this structural model is wrong," he said Textbooks need to be adjusted " The SNARE protein produces a "fusion pore" that allows the compound to pass through the membrane that separates the cell or its subcomponents Snare produces fusion pores in all organisms that contain nuclei, from many single celled organisms to plants, animals, and humans Chapman said the fusion pores and the SNARE protein that produced them are likely to have evolved a billion years ago This means that the structure and function of these fusion pores play an important role in biology "Some people think of cells as a bag of protoplasm, but it actually contains hundreds or thousands of organelles, each surrounded by a membrane," he said All of these organelles contain or process various substances and respond to numerous signals In order to excrete or ingest substances, these organelles need to form fusion pores on the membrane " According to the traditional view, when the fusion pore is formed, the SNARE protein is locked in place by a zipper like function, resulting in a structure that is basically not closed In other words, they form a kind of pipe, that is to say, a kind of "dumb" connection structure formed by passing through the membrane which can not be penetrated under normal circumstances Today, however, Chapman's team has confirmed that these fusion holes function less like pipes and more like highly complex, sensitive, and fast acting valves that can open and close thousands of times per second The relevant research results were published online in the nature Journal on January 31, 2018, with the title of "dynamics and number of trans SNARE complexes determine nascent fusion pool properties"   "Our research shows that the old idea that SNAREs assemble into compounds and then fuse is incorrect," Chapman said Instead, snare zipped up and unzipped, facilitating the dynamic change of these fusion holes after opening " The new study, based on a device designed by Chapman and his colleagues, is the first to accurately record the opening and closing times of such fusion holes Based on the number of SNARE proteins in this fusion pore and its diameter, they found that the fusion pore may be almost completely closed It may turn off, but it turns on every half second or so It may do the opposite Or it might mimic traditional wisdom and keep it on Chapman said, "fusion holes have unexpected flexibility and unexpected dynamic changes They have always been considered open or closed Signals are transmitted through these fusion holes, or not However, when we study them on the time scale of microseconds, we observe some unexpected things When there are three SNARE proteins, they open quickly, but most close When there are five snares, they are turned on most of the time, but they are turned off briefly When there are seven snares, they are mostly open " Chapman said that without the membrane fusion caused by these fusion pores, many substances produced in the cell or its organelles would be trapped Membrane fusion is a fundamental problem for organisms with nuclei, including yeast When people think that the human brain contains 10 to 15 synapses, countless fusion holes will form in our brain in one day Only now do we begin to understand the structural and dynamic properties of these mysterious nanoscale molecular machines " In the nervous system, the fusion pore is the basis of signal transduction, which transports chemical information from axons of one neuron to another through a short gap The fusion pore is also the basis of other aspects of biology, such as postprandial insulin release and virus invasion of target cells The key to this discovery is a device built by the co authors of the paper, Huang Bao and debasis DAS, postdoctoral researchers of Chapman laboratory, with the help of Yihao Jiang and Baron Chanda, which can measure the current flow in the recombinant fusion pore generated by the purified components Chapman said, "Huan and debasis can accurately measure the properties and behaviors of individual artificial fusion holes We are able to measure the opening of fusion holes at an unprecedented time resolution (less than one thousandth of a second) And these people are ahead of the world in these precise measurements " Previously, the fusion hole opening was measured in seconds, Chapman said, but better resolution makes the current results more complex and interesting "The question we're going to ask is," does the number of SNAREs used to promote membrane fusion affect results? " The answer is yes, but the nuances depend on the number of SNAREs in the fusion hole and may also depend on many other factors " Other channels that allow molecules and ions to pass through the cell membrane lack this flexibility, Chapman said "Biology could have designed fusion holes that always require the same number of SNAREs, but it didn't." It's self-evident that evolution chooses based on utility, and these common structures are those that work well Given the fact that the fusion pore is found in all organisms with nuclei, "we think it has a wide range of effects on cell to cell communication," Chapman said Chapman said the new complexity of the relationship between the fusion pore structure and the open point points points to several interesting possibilities A transient "leak" of the inclusion's fusion pore may make the receptor cell insensitive to signals For example, glutamate, as a neurotransmitter, normally stimulates the cells that receive it If the fusion pore opens quickly, a small leakage of glutamate may desensitize nearby receptor cells rather than activate them, leading to inhibition rather than activation "It seems contradictory, but it's a new function for the classic excitatory neurotransmitter," Chapman said
Chapman acknowledges that this idea is controversial, but similar results have been observed in the fusion pores that transport adrenal secretion "When the secretory cells are stimulated with low intensity, the fusion pore is very small, and only small molecules such as adrenaline and similar hormones are released If the fusion pore is stimulated with high intensity, it will open, allowing the release of larger peptide hormones, which play distinct roles in the peripheral nervous system So the size of the fusion pore determines the function of these cells " Chapman added that the results of these fusion holes were so surprising that the reviewers asked the researchers to carry out "another complete experiment" using yeast snare Chapman said, "we found the same result If you change the number of proteins, you change the nature of the opening of this fusion pore We think we may have encountered a new principle of membrane fusion If the fusion hole is very small, then there will be a different physical outcome, rather than starting to expand forward, releasing all the signals immediately This is not even a behavior that we can guess, until we achieve this kind of time resolution measurement, which allows us to see exactly what happened It's not all or nothing, yes or no, it's gradually changing " He concluded that these results could be widely used because fusion holes are ubiquitous "The behavior of this protein complex, which regulates almost all membrane fusion events, has been shown to be quite intelligent There are some strange things in biology This is a more detailed way to communicate with each other "