Phosphoinositides in ciliary transport and ciliopathies
2018
Cilia are finger-like protrusions that function in the detection and processing of a wide variety of signals. In vertebrates, they are intimately involved in early embryonic patterning, the differentiation and function of sensory neurons, morphogenesis and physiology of duct epithelia, cell motility and metabolism. Lipid composition of the ciliary membrane and its contribution to cilia function is one of the least studied areas of cilia biology. Here I use a collection of transgenic lines to determine the phosphoinositide content of the ciliary membrane and to test the role of phosphoinositides in cilia morphogenesis and function. My studies reveal that specific types of phosphoinositides are found in the ciliary membrane and that their content plays an important role in cilia morphology and function. Moreover, I generated a zebrafish model of a human ciliopathy to test whether some aspects of its mutant phenotype can be alleviated by manipulating the phosphoinositide content in the ciliary membrane. Finally, my studies developed a method that is generally applicable to the manipulation of ciliary content of other PIs in a living vertebrate using other enzymes.
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