Cytosolic calcium increases in response to ciliary bending when TRPV4 is present (left), but not when it is absent (right).

You'd think that something as dramatic as a bending cilia would be easy to sense, especially if your own activity depended on it. But the ion channel TRPP2 is oblivious to the cilia movement that activates it, and depends on another channel to relay the information, Köttgen et al. report.

In the kidney, bending of the cilia in response to the flow of fluid through the nephron tubule triggers intracellular calcium transients, setting off multiple response pathways. This cilia deflection-induced calcium increase requires the ion channel TRPP2. But TRPP2 is not itself a mechanosensor. That role, it turns out, is played by another channel called TRPV4.

TRPV4 is similar in sequence to a worm mechanosensory channel, is expressed in the kidney, and has been shown to associate with cilia. With that in mind, the authors investigated its relationship with TRPP2. They found that the two proteins both physically and functionally interacted and that blocking TRPV4 abrogated flow-triggered calcium transients.

Mutations in TRPP2 lead to cysts throughout the kidney, liver, and pancreas. It had been assumed that the primary step in polycystic disease pathogenesis was the loss of mechanosensation and downstream calcium transients. But while absence of TRPV4 abolished calcium increase, neither zebrafish nor mice deficient in TRPV4 developed cysts. This suggests that TRPP2 has an unknown function in addition to triggering calcium transients.

Köttgen, M., et al. 2008. J. Cell Biol. doi: