How is it possible to locate the tiny connection points between the cell organelles?
No man is an island, he is all of his own accord; "Every man is a piece of land, a part of a great land," wrote the English poet John Dunne in the 17th century (Hebrew translation: Rami Ditzni). Similarly, the organelles - the biological structures that make up the living cell - are not separate islands that float in the cellular fluid , to each his own. With the help of a unique method, the scientists of the institute revealed Weizmann discovered new connection and launch points between cell organelles that connect to each other through tiny "strips" the results of the study were published recently In the scientific journal Nature Communications.
The organelles are distinct parts of the cell, each of them is surrounded by a membrane, and each one has a unique role: the nucleus contains our genetic material, the mitochondria convert energy, the intraplasmic reticulum sorts proteins intended for secretion, the lysosomes break down proteins, and so on. In a previous study, Prof. Maya Shuldiner, from the Department of Molecular Genetics, discovered several points of connection between organelles. However, due to their small dimensions - only a few tens of nanometers long - the connection points are not visible in normal microscope images, and therefore it is difficult to locate all the points that are assumed to exist.
Prof. Shuldiner, along with faculty scientist Dr. Einat Salzkaber, and research student Nadav Shai, decided to take a new approach to locating the connection points, using a fluorescent protein. The scientists coated half of the protein with one of the organelles in the Shemer cell, and connected the other half to other organelles in the cell. When two organelle membranes came into contact with each other, the two halves formed one whole protein - and a glow, which you can see in a normal fluorescence microscope. Since the yeast cells are grown in Prof. Schuldiner's laboratory in thousands of "barria" and scanned under the microscope automatically, this method made it possible not only to locate points of contact between several different organelles, but also to scan all the proteins in the yeast in an attempt to locate connecting "bands" potentiality.
"If until a few years ago we thought that organelles floated in the 'soup' of the cell, while collecting messages floating in this 'soup', now we know that each organelle has its own position in the cell, and this position is determined by a network of 'bands' which also serves A direct means of transferring substances through physical contact"
In this way, the researchers were able to map the physical connections between several main organs, and find four completely new connection points. "We found that all the organelles we tagged were able to maintain connections with all the others," Shay says. "The ligaments that connect the organelles organize the cell and assign a location to the various organelles. For example, two organelles that need to work closely together will naturally be tied together in a certain area of the cell. Furthermore, the connection through the ligaments appears to be an effective way to transfer from organelle to organelle materials or messages that may be harmful if they reach the wrong place."
Later, the research team decided to examine a specific connection point, the one that links the peroxisome organelle to the mitochondria. The peroxisome breaks down fats, both for using them as raw materials for energy conversion in the mitochondria and for removing toxic fats from the cell. For example, the lipids that make up the myelin coating on nerve cells can be toxic if there are large amounts of them. Thus, if the peroxisome does not function properly in the cells that produce the protective layer, this may cause severe nerve damage, and often even the death of the patient. In general, "peroxisomal diseases" - such as X-ALD described in the movie "Lorenzo's Fat" - are genetic diseases that have devastating consequences.
Most of the broken down fats are transported directly to the mitochondria. Hence, the peroxisome needs an efficient way to connect to the cell's energy converter. The research group was able to identify two genes that produce the "bands" that connect the mitochondria to the peroxisome. With the help of a team of experts in peroxisomal diseases from the Medical Center of the University of Amsterdam, the Netherlands, the group identified the function of the connection point: the transfer of lipid breakdown products to the mitochondria for their use. The research revealed, therefore, that certain peroxisomal diseases are actually connection disorders, that is, a condition in which the peroxisome is unable to transport the products of fat breakdown to their destination.
"When it comes to basic functions," explains Dr. Salzkaber, "yeast cells are almost identical to our cells. So it is likely that the connections and extensions that we saw in the Shemer cells can also be found here. Another advantage is that yeast is very easy to grow, they have fewer genes, and there is a lot of extensive research in relation to them. After we identify the role of the proteins in Shimar cells, we know where to look for them in human cells." Shi adds: "Many laboratories have already adopted our method to discover new intracellular connections. Since the method is based on tools found in most laboratories, and in light of the fact that it is also valid for human cells, we believe that it will be very useful for genetics and cell biology researchers."
"The discovery of contact sites within the cell in recent years has opened our eyes," says Dr. Salzkaber. that each organelle has its own position in the cell, and this position is determined by a network of 'strips' which also serves as a direct means for the passage of materials through physical contact." Prof. Shuldiner adds: "Understanding the manner of organization of the cell organelles and the interrelationships between them revolutionized the field of cell biology. We believe that the new method we developed for revealing connection points between organs will lead scientists in the coming years to new and interesting paths."
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One response
The "bands" are microtubulin? If not, what are they made of?
The latter move closer and further apart with the help of the instability (disconnection) of the fibers?