Researchers in University College Dublin (UCD) led by Conway Fellow, Dr Oliver Blacque have revealed new information about a gene implicated in Joubert syndrome and related cerebellar disorders (JSRDs) that are characterised by blindness, bone abnormalities, cystic kidneys, developmental delay and loss of muscle tone and control. The findings from this research, which is funded by Science Foundation Ireland, have been published today in a leading science journal, Journal of Cell Biology.
One of seven genes associated with JSRDs, Arl13b codes for a protein already known to play roles in the formation and/or function of cilia, which are hair-like projections extending from the surface of the cell. However, the precise molecular details of what exactly Arl13b is doing in cilia have remained unclear.
To address this question, the UCD team asked what this gene is doing in the cilia of tiny worms (Caenorhabditis elegans), and collaborated with scientists in the University of Tokyo who conducted parallel experiments in cultured human cells.
Together, they confirmed that Arl13b proteins uses lipid anchors to associate with the ciliary membrane. The UCD scientists then went on to demonstrate in C. elegans how disrupting the function of this protein can cause the ciliary membrane to bulge and become misshapen as well as affecting the ability of other proteins to properly distribute within the ciliary membrane.
They also found that a fully functional Arl13b protein is needed for the normal functioning of a protein transport system in cilia. This intraflagellar transport system makes contact with the ciliary membrane. These results have led the team to propose a new working model for Arl13b, where it functions at the ciliary membrane to regulate important ciliary membrane properties such as shape, transmembrane protein distributions and IFT.
Up to only 20 years ago, many believed most cilia to be redundant cellular organelles that have fallen victim to mammalian evolution - a type of cellular appendix. However, scientists now know that these cellular antennae serve fundamental roles in many motility and sensory functions, including signalling pathways critical to development.