We know a lot about how cells work and about the organelles they contain (the nucleus, mitochondria, endoplasmic reticulum and so on). However, scientific knowledge is always changing. Even when something seems to be well understood, new information can be uncovered that changes our view. That’s exactly what happened in the 1960s when scientists first noticed a new organelle under the microscope. After many years of research, we now know that this organelle (the primary cilium) is an important ‘antenna’ that helps cells to sense their surroundings.
Associate Professor Tony Poole from the University of Otago has been trying to understand how the primary cilium works since the 1980s, using a variety of microscope techniques. In his latest work, he’s building a 3D computer model of the primary cilium in cartilage cells.
A needle in a haystack
The primary cilium is tiny, and that’s the main reason it remained undiscovered for so long. At just 200 nm wide, it’s right on the resolution limit of light microscopes, making it virtually impossible to see. It is visible through the transmission electron microscope (TEM) but is still very difficult to spot. This is because there’s only one on each cell, and it could be lying in any direction. Even when it was eventually noticed, nothing was known about what, if anything, it did.
An ‘antenna’ function for the primary cilium
Just like animals and plants, cells respond to what’s happening outside their own boundaries by adapting their behaviour. The kind of information they need and the way they respond to it depends on what kind of cell they are. For instance, cells in the immune system receive signals from their surroundings to tell them that infection has occurred, and they respond by going to the infection site. Many cell types use information about the level of nutrients in their environment to determine whether they grow and divide.
Back in the 1980s, Tony suggested that the primary cilium might work as a cellular ‘antenna’, giving the cell information about its surroundings and enabling it to respond. At first, this idea wasn’t well received, but most scientists now agree that the primary cilium does work as an antenna.
Sensing load and strengthening joints
Tony works on the cells that make cartilage in our joints (chondrocytes). These cells need information about how much load a joint is carrying so they can make more cartilage to strengthen the joint if required. Tony has shown that it’s the primary cilia in chondrocytes that give the cell this information.
How do the primary cilia know how much load is being placed on a joint? By looking closely at individual cilia under the TEM, it’s possible to see that they are directly connected to the collagen outside the cell. When the collagen flexes under a heavy load, the cilia are pulled about. This pulling sets off a chain of signals that tell the cell to produce more of the proteins that make up cartilage (such as collagen) to give the joint more strength.
Longer and shorter
Tony has also discovered that the primary cilium on a chondrocyte can become shorter or longer. This change in length seems to be the cell’s way of adjusting signal strength, in the same way you’d put your car radio antenna up if the radio signal wasn’t strong enough. Primary cilia on chondrocytes get shorter when the joints are under heavy load and grow again when the load is less.
The next step: a 3D view of the cilium
Recently, Tony has been trying to build up a three-dimensional model of the cilium. He especially wants to understand more about how the cilium interacts with molecules outside the cell (such as collagen). To build the model, Tony and PhD student Mike Jennings have been using electron tomography – a form of TEM that provides 3D information about subcellular components.
It’s a slow process (Mike has worked on the model for a year!), but it’s worth it. The model has helped Tony and Mike to understand aspects of cilium structure that couldn’t be worked out from standard microscopy approaches.
Nature of science
When scientific understanding is challenged by new information, it can take time for ideas to change. In the case of the primary cilium, there was initially resistance to the idea that it had an important role in cell function. Now, it is widely accepted that it co-ordinates much of the information that cells receive from their surroundings.