Cells’ internal gauge to monitor own size

Varuni Ankolekar, Clinical Data Manager at Quartesian

Researchers have identified that cells have their own internal gauge to monitor their own size. The key protein behind this, or in other words, “cells’ internal gauge” is KRP4 protein, which is responsible for regulating cell size.

What is a Cell? What are the different components of a cell?

A cell is a basic structural and functional unit of all living organisms, except viruses which do not have a usual cellular organization. A cell comprises of three parts: the cell membrane, the nucleus (made up of nuclear membrane, Nucleoplasm, Chromatin, Nucleolus), and, amid the two, the Cytoplasm (Cytoplasmic organelles are mitochondrion, ribosomes, endoplasmic reticulum, Golgi apparatus, and lysosomes).

What is cell division? Why do cells divide?

Cell division is a process where a parent cell divides into daughter cells. Cell division occurs in prokaryotes as binary fission, budding, and in eukaryotes as mitosis (equational division) and meiosis (reductional division). Phases of eukaryotic cell division (Interphase, Prophase, Metaphase, Anaphase, Telophase, Cytokinesis).

There are many reasons why cells divide. Cells divide to substitute the old, dead, or damaged cells. Cell division is required for the growth of organisms. When organisms grow, it is mainly due to the division of cells to produce more and more cells. The human body encompasses trillions of cells. Nearly two trillion cell division is observed in humans every day.

Although the cells were discovered several years ago, the question of how these cells control their size was unknown until today.

Mystery of how cells regulate their size revealed:

Even though it was discovered that DNA could be used as a basis for cell size, it was unclear how the cells read and make use of this data. DNA is a blueprint that is used to collect the appropriate amount of protein and is diluted before the cell division. The cell size would depend on how much the cells have grown and how frequently they divide after reaching a certain cell size before division. The question is how the cells examine what their size is.

Robert Sablowski and the team decided to see what is behind the curtain by exploring the meristematic cells of plants that continuously grow and divide. The division of these cells is not only seen as unequal but also, seen to have managed to stay within range of sizes for a long duration.

Careful observations helped them understand that initially cells are of distinct sizes, but they turn out to be uniform when the cells are ready to replicate their DNA.

Let us now see, how it was found out what makes the cells to be of equal size and who is the cells’ internal gauge. KRP4 (KIP-related protein 4) is a protein that plays a key role in delaying the beginning of DNA replication. The team noticed that the same amount of KRP4 is seen in all the cells irrespective of cell size. Cells are consistent in sizes as others regardless of the size of the newborn and align themselves in a narrow size range. If the original size of the cell is too small, a higher concentration of KRP4 lags the beginning of DNA replication and if cells are too big, KRP4 is diluted to restrict further growth.

Now the question that arises is, what ensures that the same amount of KRP4 is received in all cells? It turned out that KRP4 travels on DNA during cell division, which gets copied identically in daughter cells. To ensure that the KRP4 is accumulated in the mother cell in correct proportion to the DNA content, any excess KRP4 that is unbound to the DNA is destroyed before cell division by another protein known as FBL17. The amount of KRP4 would be proportional to the DNA content of the cell. This was proven by Mathematical models and using gene-edited mutants with the diverging amount of these genetic components.

Researchers are further keen to understand how KRP4 associates and dissociates chromosomes during cell division if the mechanism is modulated in different cell types to generate different typical sizes. Thus, this is the cells’ internal gauge responsible for maintaining cell size.

Many organisms have been found to have KRP4 proteins which are also crucial to regulate cell size in human cells, hence could apply to animal and human biological kingdom. Future experiments will seek out the answers to these perennial questions about cells.

Also read: Importance of polymers against Coronavirus disease

Reference:

1. D’ario M., Tavares R., Schiessl K., Desvoyes B., Gutierrez C., Howard M., Sablowski R. (2021). Cell size controlled in plants using DNA content as an internal scale. Science. Vol. 372, Issue 6547, pp. 1176-1181. DOI: http://10.1126/science.abb4348

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