Loading
Cilia and flagella are tiny-hair-like projections from cells that play important roles in motility and in sensing changes in the cellular environment. Whilst we are familiar with their role in motility, the mechanisms cilia use to sense environmental stimuli and transmit this information to the rest of the cell are less clear. Cilia are built at the tip using a process known as intraflagellar transport (IFT), which enables proteins to be moved along the cilium to the site of assembly. It has also been shown that IFT plays an important role in ciliary signalling, as many important receptor proteins localise to cilia and are moved into and out of the cilium by IFT. Disruption of ciliary signalling due to defects in IFT can lead to human diseases and developmental problems, and it is therefore important for us to understand how intraflagellar transport is regulated. Using the motile green alga, Chlamydomonas, as a model system to study ciliary signalling, we recently discovered that IFT may be regulated by calcium signalling. Many environmental stimuli trigger ion channel proteins in cell membranes to open and cause a rapid influx of calcium ions (Ca2+) into cells. This results in elevated Ca2+ within the cell, which triggers various signalling cascades depending on the nature of the stimulus. Ca2+-dependent signalling processes are central to both the motile and sensory roles of cilia, but we know very little about the nature of these Ca2+ elevations and how they act to regulate ciliary processes. The discovery that Ca2+ signals are regulating IFT therefore links two very important processes in cilia and should help us understand much more about how these organelles sense and respond to their environment. We have used Chlamydomonas to develop a novel microscopy technique that allows us to simultaneously image Ca2+ and the movement of IFT particles in flagella for the first time. Chlamydomonas is currently the only organism in which this technique is possible and this unique ability will allow us to directly examine the mechanisms underlying this novel signalling process. Chlamydomonas can glide along solid substrates on its flagella by using IFT to move proteins in the flagella membrane. Gliding is coordinated by flagella Ca2+ signalling. Ca2+ elevations in one flagellum cause the IFT particles to dissociate from the flagella membrane and stop pulling the cell along. This gliding process is therefore an excellent model system in which to study how Ca2+ signalling regulates IFT to control the movement of flagella membrane proteins. Although we know that Ca2+ regulates IFT, we don't yet know how this happens. This proposal seeks to identify the specific cellular mechanisms responsible. Firstly, we will examine how Ca2+ signals are generated in Chlamydomonas flagella, looking at the ion channels responsible and at mechanisms that restrict Ca2+ elevations to individual flagella, to enable specific control of IFT during the regulation of gliding motility. We will then examine the different types of Ca2+ elevations that are used to regulate IFT, using mathematical models in combination with experimental data to help us understand the rapid changes in Ca2+ concentration inside the flagellum. Finally, we will look at how Ca2+ actually causes the IFT particles to dissociate from the flagella membrane, by identifying specific flagella proteins that may bind to Ca2+ and disrupt this interaction. The process of IFT is highly conserved amongst eukaryotes and it is likely that Ca2+-dependent regulation of IFT influences the movement of many ciliary proteins, including those involved in developmental signalling pathways relating to human genetic diseases. Therefore the results from our studies in algae will provide insight into how ciliary signalling is regulated in many different organisms, including mammals, and shed light on the many different roles cilia play in sensing and responding to the cellular environment.
<script type="text/javascript">
<!--
document.write('<div id="oa_widget"></div>');
document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=ukri________::8a19e3c9b8e492a8cf1a8b941cf97801&type=result"></script>');
-->
</script>