Since scientists discovered cells under a microscope over 350 years ago, they have found that each type of cell has a characteristic size. From tiny bacteria to neurons a few inches long, size matters in how cells function. The question of how these building blocks of life regulate their own size, however, has remained a mystery.
We now have an explanation for this long-standing biological question. In a study looking at the growth tip of plants, researchers show that cells use their DNA content as an internal gauge to gauge and adjust their size.
Professor Robert Sablowski, group leader at the John Innes Center and corresponding author of the study, said: “It has long been suggested that DNA could be used as a scale for cell size, but it was not. not clear how cells could read the scale and use the information. The key is to use DNA as a template to build up the right amount of a protein, which must then be diluted before the cell divides. It’s exciting to find such a simple solution to a long-standing problem. problem.”
The average cell size is the result of a balance between the amount of cells that grow and the frequency with which they divide in half. It has long been clear that cells reach a certain size before dividing. But how can a cell know how much it has grown?
A good place to study this question is in the shoot meristem, the growing tip of the plant, which provides new cells to make leaves, flowers, and stems. Meristemic cells are constantly growing and dividing. Their divisions are often not equal, producing cells of different sizes. Over time, these differences should build up, but the meristem cells stay in a narrow size range for long periods of time.
In this study, which appears in Science, researchers at the John Innes Center have carefully followed the growth and division of meristemic cells over time. They found that although cells can start their lives with varying sizes, just when cells are ready to replicate their DNA (a necessary step before cell division, because each new cell needs its own copy of the DNA), most of the initial variability in cell size has been corrected.
They then monitored a protein called KRP4, whose role is to delay the onset of DNA replication, and found that, regardless of their initial size, cells are always born with the same amount of KRP4. This means that when a cell is born too small, it receives a higher concentration of KRP4, which delays its progress towards DNA replication, allowing time for the cell to catch up to the same size as other cells. Conversely, if a cell is born too large, KRP4 is diluted so that it can move quickly to the next stage without growing further. Over time, this keeps the meristem cells in a narrow size range.
But what makes sure cells start with the same amount of KRP4? It turned out that when cells divide, KRP4 “spins” on DNA, which is given in identical copies to each newborn cell. In this way, the initial amount of KRP4 becomes proportional to the DNA content of the cell. To ensure that KRP4 accumulates in the mother cell in proportion to the DNA content, any excess KRP4 not bound to DNA is destroyed before cell division by another protein called FBL17. Mathematical models and the use of genetically engineered mutants with varying amounts of these genetic components have confirmed the mechanism.
Professor Robert Sablowski explains this process: “One riddle we had to solve is how a cell can tell by how much it has grown when most of the components of a cell together increase in number and size, so that they cannot be used as a fixed ruler to measure height. One exception is DNA that exists in the cell in discrete amounts – its amount doubles precisely before cell division, but it does not vary with cell growth.
Future experiments will seek to explain exactly how the regulatory protein KRP4 associates and then dissociates from chromosomes during cell division. The researchers also want to understand if the mechanism is modulated in different types of cells to produce different average sizes.
The results may explain the relationship between genome size and cell size – species with large genomes, and therefore a lot of DNA in their cells, tend to have larger cells. This is especially important in cultivated plants, many of which have been bred to contain multiple copies of the genomes found in their wild ancestors, leading to larger cells and often larger fruits and seeds.
Components of the genetic mechanism that includes KRP4 are present in many organisms, and it has been suggested that these components are important in regulating the size of human cells. Thus, the mechanism discovered in the study may also be relevant in all biological realms, with implications for animal and human cell biology.
Source of the story:
Material provided by John Innes Center. Note: Content can be changed for style and length.