Introduction to the cytoskeleton
Often more absent than not in biology student cell diagrams, the cytoskeleton is usually forgotten when listing the cellular components. However, the cytoskeleton is a crucial structure involved in a myriad of processes which occur all day, everyday, as you will see shortly.
«Somebody pinch me», you might be saying because of your astonishment at this claim. Well, if you do get pinched, ask yourself: why do the millions of cells on your skin stay together and not break apart? Collagen, a type of cytoskeleton protein, maintains cells attached to one another to resist tearing forces, such as those in the pinch. Furthermore, the muscles that you are using when you breathe, move your hands or run a marathon depend on actin and myosin which are also cytoskeletal proteins. If you are intrigued by this and want to learn more, keep on reading!
Types of cytoskeleton
Cytoskeleton is an umbrella term for the dynamic proteins which are used in the cell for movement and structure maintenance. In reality, there are three types of cytoskeletal proteins, each with their own distinguishing characteristics and functions: actin filaments, intermediate filaments and microtubules.
- Actin filaments. These are the smallest kind with a 7-9 nm diameter. Cell movement, muscle contraction and cell organisation depend on actin subunits which are what make up the filaments. The actin protein is a 4-lobed structure that is able to bind and hydrolyse ATP.
- Intermediate filaments. As the name suggests, these are thicker than the actin filaments, but thinner than the microtubules, with a 10 nm diameter. According to the type of protein which makes up the filaments, they can have different properties, but their main role is to provide stability and prevent tearing when forces are applied to the cell (such as the collagen example in the introduction).
- Microtubules. At 25 nm in diameter, these thick and hollow tube-like structures are crucial for cell division, organelle distribution and cilia and flagella, involved in cell motility. The α-tubulin and β-tubulin proteins are the monomers that make up microtubules. Although they are very similar since they both bind GTP, only β-tubulin can hydrolyse it.
How is the cytoskeleton formed?
Now that you have seen the kinds of cytoskeleton that exist, you might be wondering how it is made. Actin filaments and microtubules are built in similar ways, in something that is called a «head-to-tail» assembly. Meanwhile, intermediate filaments have a completely different way of connecting to each other to form long, resistant, rope-like structures.
Actin and microtubules: Head-to-tail assembly
Firstly, both actin subunits and α-tubulin and β-tubulin are polar. In this context, this does not mean they are charged positively or negatively. Instead, it means that they can be distinguished by having a front end, or head, and a back end or tail. This polarity accomplishes two things: it causes the subunits to bind to each other as if they were Lego pieces and it makes one end of the structure the «minus» end, while another is called the «plus» end.
After many experiments on the formation of actin filaments it was shown that actin subunits bind faster to the plus end than the minus end. The reason for this was ATP hydrolysis. Towards the plus end, there remained a few actin subunits which were still bound to ATP, while those at the minus end were all bound to ADP. The conformation shift caused by the hydrolysis made it harder for new subunits to bind the minus end. The same happens in microtubules.
This phenomenon is known as dynamic instability, because, in the same way that the subunits bind to one end better than the other, they unbind more easily from the minus end than the plus end.
Intermediate filaments are made up of non-polar subunits. The specific subunits depend on the kind of filament: keratin, lamins, vimentins or neurofilaments. Each one of these categories will have subunits with distinct N- and C-termini sequences (the start and finish of a protein) so that they bind only to those with similar characteristics. For instance, a keratin monomer should not be able to bind to a lamin monomer.
The proteins that make up intermediate filaments are rope-like and are made up of coiled coils. Even though it might seem that I repeated myself twice, coiled coil is the correct term. This special type of secondary structure is made up of two or more α-helices, which in turn wrap around each other making an even bigger coil.
Therefore, the protein of the intermediate filaments assembles first into a homodimer. Next, the N- and C- termini of one homodimer interact with a central part of the coiled coil of another. Lastly, these staggered tetramers join together at their ends to form protofilaments. The intermediate filaments are a group of these protofilaments.
Functions of the cytoskeleton
The principle underlying most of these functions is the ability of the cytoskeletal polymers to associate and dissociate rapidly. Ironically, ATP (and GTP) are being used up to maintain the instability of the cytoskeleton and not keeping it rigid as one might suppose. However, this is what allows the cell to be motile and flexible by forming the structures in one direction or in another in response to stimuli.
As you will read, the cytoskeleton is involved in many processes- it would be impossible to describe each one in detail in a short article. Thus, I will only provide a brief description of some functions, showcasing interesting information along the way.
By far, the most important function of the cytoskeleton is the role it plays in cell division when microtubules of the mitotic spindle attach to the chromosomes (via the kinetochores). Once each sister chromatid has been bound to a microtubule, they begin to depolymerise, which causes them to shorten and pulls the chromosomes apart.
Furthermore, actin and myosin are also involved in cell division during a later phase, known as telophase. At this point, the cell is about to form the two daughter cells and it adopts a kind of peanut or number 8 shape. The location where they will pinch off one another is called the cleavage furrow and it comprises of an actin ring bound to myosin which together promote contraction.
Tense cell cortex
Have you ever thought about how the cell stays in the shape of a sphere and does not collapse on itself like a deflated beach ball? Another function of actin is maintaining the integrity of the cell membrane by forming the cell cortex. Together with an accessory protein called filamin, a gel like substance is created under the cell membrane which keeps it stiff enough to prevent it from caving in.
In a similar way that actin and filaments keep the cell tense, the nucleus has its own proteins which help it achieve the same rigidity. These are known as nuclear lamins and are a type of intermediate filament.
Even though it might seem like an unimportant protein, it has been shown that mutations in lamin A (a subtype of lamin) cause Hutchinson–Gilford progeria syndrome. This fatal disease induces rapid aging in children and often involves heart failure, as well as other organ problems.
Transportation of substances
Microtubules are analogous to railroads in the sense that they both provide a guide for other vehicles to move along them. In the case of cell biology, small motor proteins walk along the microtubules in specific directions attached to cargo, which can be anything from a vesicle to an entire organelle!
The most important types of motor proteins are kynesins (which move from the minus end towards the plus end) and dyneins (which move in the opposite direction). Unsurprisingly, what triggers the movement of these proteins is ATP hydrolysis.
Flagella and cilia
Lastly, I will discuss the movement of flagella and cilia. These structures are prolongations of the cell membrane which contain microtubules and other motor proteins. When dyneins move along the microtubules, they generate enough tension to later snap back into the position they were in before, creating movement.
The internal organization of these components is what allows this mechanism to succeed. Nine pairs of doublets surround a central microtubule, while the dyneins are bound to the cell membrane and the cytoskeleton. In this way, the cilia or flagella can remain flexible without breaking.
In this article, you have discovered what the cytoskeleton is, how it is formed and what some of its main functions are. As I mentioned previously, this is only an abbreviated list- the cytoskeleton is much more versatile and ubiquitous in cells. I hope you have gotten a better idea of the way in which different types of cytoskeleton interact with other organelles and structures. From cell division to transporting substances, remember that the cytoskeleton plays a part in almost every living process!
- Cover image: Illustration by David S. Goodsell
- Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K. and Walter, P., 2021. The Cytoskeleton. [online] Ncbi.nlm.nih.gov. Available at: https://www.ncbi.nlm.nih.gov/books/NBK21051/
- Fletcher, D. and Mullins, R., 2010. Cell mechanics and the cytoskeleton. [online]. Ncbi.nlm.nih.gov. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851742/
- Bretscher, A., 2000. The cytoskeleton: from regulation to function. Ncbi.nlm.nih.gov. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1083793/
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