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Gaining insight of trafficking pathways within cilia

Gaining insight at the molecular level of the intracellular trafficking pathways operating in cilia may shed light on the causes of multisymptomatic cilia-related disorders such as polycystic kidney disease, Bardet-Biedl syndrome and retinitis pigmentosa.

New research published today as an article in the Cell Press journal, Current Biology by UCD researchers led by Conway Fellow, Dr Oliver Blacque in collaboration with colleagues in Brandeis University, USA has shown that endocytic membrane transport genes facilitate protein and membrane transport in C. elegans sensory cilia.

These hair-like projections from eukaryotic cell surfaces bear the responsibility for motility, sensation and developmental signalling. The functional integrity of cilia depends on intracellular transport pathways.

With no protein synthesis occurring in cilia, proteins must be trafficked to the organelle but this process is poorly understood. Roles for exocytosis in regulating cilary protein and membrane transport have been described previously but until now there was only limited evidence that endocytosis events are also involved. 

During endocytosis plasma membrane and associated proteins bud off the cell surface as internalised vesicles, a process important for various cellular functions such as regulation of membrane protein activities and uptake of extracellular molecules.

Pictured: Transmission electron microscopy image showing the ciliated dendritic ending of one sensory neuron in C. elegans. In worms with disrupted clathrin adaptor 2 complexes (endocytic mutant), the periciliary membrane (red) that exists immediately beneath the ciliary membrane (green) is massively expanded compared to wild type worms. This indicates a defect in periciliary membrane recycling.

Commenting on the research, Dr Oliver Blacque said, "This is the first demonstration in any multi-cellular organism of a functional connection between endocytosis and cilia. It provides a springboard for future work into how molecular transport systems organise the various structures and functions of cilia.

Furthermore, because ciliary defects are implicated in more than a dozen multisymptomatic diseases, for which more than 80 genes are now associated, our work helps to understand how intracellular trafficking pathways contribute to disease aetiology."

The research in Dr Blacque’s laboratory was funded through Science Foundation Ireland and the EU 7th Framework Programme.

Reference
Kaplan et al., Endocytosis Genes Facilitate Protein and Membrane Transport in C. elegans Sensory Cilia, Current Biology (2012), doi:10.1016/j.cub.2012.01.060