Scientific highlights

19.06.2020

Size matters after all...

... at least for cells
 
Every human being has an individual body size. Some are small, and some are huge like Dirk Nowitzki. However, compared to the enormous variability in size we find between different animals – think for example about flies or elephants – humans are rather homogenous in height. If we look at cells in the human body, we find that there is an enormous variability of cell sizes, from the neuron with immense axons to smaller skin cells. However, for the same cell type, for example within a given tissue, cells are rather uniform in size. The size of cells and the size of their subcellular organelles are well-defined, and it is important for the cell’s function -and therefore for organs too- that the correct sizes are maintained. But how do cells manage to maintain their size and that of their organelles? In a new study published in Nature Communications, Dr. Igor Kukhtevich, Dr. Kurt Schmoller, and colleagues from the Institute of Functional Epigenetics at the Helmholtz Zentrum München studied the septin ring as a model to answer this question.

@Epigenetics@HMGU; Kukhtevich et al., 2020, Nat Comm

Size is a dimension that can be measured in length, height, diameter, width, volume, mass, and many more. Size determines our everyday life. How tall are you? Do you want a bigger pizza piece? Is my abstract long enough or too long? What clothing size do you wear? And so on… We always try to control our body size and do not like if it changes. Likewise, each cell of our body has also to control its size and the size of its tiny organelles, because otherwise the cellular function is impaired. Similar to us humans, cells are smaller at their ‘birth’ and get bigger during each cell cycle, so when cells proliferate, they control their size by balancing cell growth, division, and cell death. Obtaining the right size has been suggested to be a major factor for the cell’s decision when to divide. While cells that are smaller at their birth have more time to grow until they divide, oversized cells divide more quickly. Not surprisingly then, cancer cells – which lost the regulation of growth and division – often have distorted and variable sizes compared to healthy cells.

Comparing tissue cells, such as the pancreatic β cells, of different individuals has revealed that, surprisingly, the size of the cells is rather constant. Taller people have just more cells than smaller ones. However, a change in organ size, if physiologically required, can be adopted by changing the cell number, the cell size, or both. For example, during pregnancy pancreatic  cells increase 25% in cell size because of the increased insulin demand of the mother. Small β cells secrete less insulin per cell compared to cells with a normal size. Moreover, bigger fat cells (adipocytes) are associated with insulin resistance and a risk factor for the development of type II diabetes, because they are less sensitive to insulin upon glucose uptake. Thus, understanding how cells regulate their size is of paramount importance to capture the complexity of disease emergence and phenotypic implications.

It is clear that the formation and maintenance of the correct cell size is physiologically relevant, but what happens with the subcellular organelles if the cell size changes? How do they adapt and ‘follow’ the changes of size in the cell they belong to? Humans can go shopping if they lose weight and clothes become too big, but cells cannot simply get a new nucleus that fits the cell size. Instead, cells need regulatory mechanisms that ensure that intracellular structures match the cell size. For some subcellular structures, it has been shown that they scale with size. For example, in C. elegans, the size of the spindle apparatus that is important for cell divisions shrinks as the cell size decreases. However, the understanding of the size-regulating mechanisms of subcellular organelles is very limited.

Dr. Igor Kukhtevich, Dr. Kurt Schmoller, and their colleagues at the Institute of Functional Epigenetics at the Helmholtz Zentrum München studied the cell-volume dependence of the septin ring formation. “The septin ring is an important structure that assembles during cell division in many eukaryotes.”, said Dr. Kurt Schmoller, the corresponding author of the publication. “The septin ring formation of budding yeast during mitosis is best-studied and it has developed to one of the most important models for understanding cell size dependency. Besides, it is a beautiful structure where we can understand self-assembly processes. Thus, we used the septin ring as a model to study the size control of subcellular structures”.

The group of researchers performed live-cell imaging analyses of yeast cells that were genetically modified in such a way that their cell volume can be controlled. In doing so, they could identify that the septin ring diameter increases with increasing cell volume and that its structure is therefore not fixed but can be adapted to the physiological needs of the cell. For example, older and bigger yeast cells had an increased septin ring diameter. Moreover, they could observe that the previously described ploidy dependence of the ring size is dependent on the cell volume. “It seems that there is an optimal size of the septin ring diameter that changes with cell size.”, added Dr. Igor Kuhktevich, the first author of the paper. “It has been shown that the size of other organelles is also cell-volume dependent, such as the nucleus. It would be interesting to find out what determines the optimal size of a distinct cellular organelle. From our results, it is clear that the septin ring diameter can be used as a powerful model to study the processes behind organelle size control.”

The findings showing that the ring itself scales with cell size pave the way for a new understanding of how organelles within the cell adapt to changes of cell size. Since changes of cell size occur as a response to environmental changes, as a consequence of diseases or during development, understanding cell size control is important for human health.

If you would like to read the full article, go here.