Intraflagellar Transport - Physiological Importance

Physiological Importance

Due to the importance of IFT in maintaining functional cilia, defective IFT machinery has now been implicated in many disease phenotypes generally associated with non-functional (or absent) cilia. IFT88, for example, encodes a protein known as Tg737 in mouse and human, and the loss of this protein has been found to cause an autosomal-recessive polycystic kidney disease model phenotype in mice. Other human diseases such as retinal degeneration, situs inversus (a reversal of the body's left-right axis), Senior-Loken syndrome, liver disease, primary ciliary dyskinesia, nephronophthisis, Alstrom syndrome, Meckel-Gruber syndrome, Sensenbrenner syndrome, Jeune syndrome, and Bardet-Biedl syndrome, which causes both cystic kidneys and retinal degeneration, have been linked to the IFT machinery. This diverse group of genetic syndromes and genetic diseases are now understood to arise due to malfunctioning cilia, and the term "ciliopathy" is now used to indicate their common origin. These and possibly many more disorders may be better understood via study of IFT.

One of the most recent discoveries regarding IFT is its potential role in signal transduction. IFT has been shown to be necessary for the movement of other signaling proteins within the cilia, and therefore may play a role in many different signaling pathways. Specifically, IFT has been implicated as a mediator of Sonic Hedgehog signaling, one of the most important pathways in embryogenesis.