The Motors Within our Cells

by Will Hartridge

cytoskeleton

It can be easy to think of the cell as a simple building block of the body containing just organelles and empty space, I think in part due to the misleading classic diagram of a cell that many are familiar with. However, in reality, the cell is much more complex and diverse than it appears, a highly specialized but crowded aggregation of components all working together in synchronous harmony. To facilitate this extreme coordination and overcome the crowded and messy nature of the cytosol a transport system is required: sometimes cells cannot rely on just diffusion, instead, a system is needed to move molecules, proteins and even whole organelles around the cell to precise locations at the correct time. Take this analogy: if the cell is a busy city with each organelle being a distinct place, for example, the mitochondria as a power station, you need roads and vehicles to transport goods around the city between locations. This is what motor proteins are for- carrying cargo along specialised tracks, known as the cytoskeleton, to locations all around the cell. This cytoskeleton, the roads of the cell if you will, is composed of a network of filamentous proteins including microtubules, intermediate filaments and actin fibres spanning the cell. It is also is vital for many other aspects of cellular function, including stabilising the cell to resist deformation and maintaining the fixed position of organelles.

motor protein animation

This mesmerising animation shows the almost anthropomorphic “walking” action of a motor protein moving its cargo along the cytoskeleton, it is fascinating how this assembly can convert chemical energy into such perceptible movement and take hundreds of successive “steps” to move its cargo to different locations within the cell.

There are a few variations of motor proteins, categorised by the cytoskeletal element they utilise and what direction they can travel in. Myosin is a family of motors that are able to walk on actin fibres. However, the rest of this article will be mainly focused on the microtubule motor proteins: kinesins and dyneins.

microtubule structure

Integral to the function of motor proteins are the tracks themselves: microtubules are polymers of the globular tubulin protein, most of which extend from organelles called centrioles out towards the edge of the cells. Due to tubulin’s dimeric structure, meaning it is made up of two individual polypeptide chains (α-tubulin and β-tubulin), when a microtubule is formed α-tubulin is exposed at one end and β-tubulin is exposed at the other end, resulting in the polarity of microtubules- negative at the end which is usually located at the centre of the cell and positive at the end which is usually located at the edge of the cell. Dyneins generally move towards the negative end (towards the inside of the cell) and the kinesins move towards the positive end (towards the outside of the cell). This means a different motor protein can be used depending on the direction that substances need to be moved in.

motor proteins from the kinesin family

Each motor protein has many different domains responsible for one function of the whole protein, typically motor domains (that are responsible for movement) are connected by a coiled-coil and hinge region to a tail domain responsible for binding to its cargo. Within a family of motor proteins, the motor domains are very similar in structure (as the walking mechanism has no need to vary), however, the tails and coiled-coil domains vary significantly depending on the type of cargo it can carry, allowing for the extreme diversity and functionality of motor proteins.

I think that explaining the full mechanism of movement is not necessary, nevertheless to summarise (for kinesin specifically): successive ATP binding, hydrolysis and release causes a conformational change in the protein that allows the “feet” (motor domains) to detach, swing around 180 and bind again- resulting in the protein taking steps of 16nm at a time along the microtubule. Conformational change means that a change in protein structure is caused by the binding of a molecule (ATP in this case).

simplified mechanism of kinesin movement

Now the structure and function have been outlined, what can these motor proteins do inside the cell?

Firstly is a function that has already been alluded to by the animation- to move vesicles around the cell, which are essentially protective coats containing the material that needs to be transported.
Motor proteins also are partly responsible for the movement of chromosomes to opposite ends of the cell along microtubules during cell division.
Interestingly, in some cases motor proteins can be used against the cell, some viruses can hijack them for self-benefit, “hitching a lift” and speeding up their replication and distribution. As soon as a virus enters a cell, some types are able to move their cores (composed of nucleic acids and proteins) to replication sites quicker in order to start replication as soon as possible. Then the microtubule network can be utilised to move components between organelles while viruses are being assembled and again to move viruses to the membrane of the cell for a quicker release.
Some fish and amphibians can change their skin colour by changing the distribution of pigment-containing organelles called melanosomes using dynein and kinesin motor proteins.
However their functions are not limited to transport: they can also be used to generate larger movements within organisms, for example, muscle contraction- where a filamentous form of myosin motor proteins are used to slide actin fibres and shorten sarcomeres (the most basic unit of muscles) to cause contraction. Motor proteins are also used in flagella and cilia movement, where dynein motor proteins induce the movement of microtubules- causing a beating motion that propels whatever it is attached to. Flagella are responsible for the movement of some bacteria and sperm and cilia are located along the exterior of the cell and can move substances across their surface (for example cilia in the respiratory system can move foreign matter, pathogens and mucus away for protection)