The primary cilium calcium channels and their role in flow sensing.

The primary cilium has been the focus of intense research since it was discovered that mutations in ciliary/basal body localized proteins give rise to a multitude of disorders. While these studies have revealed the contribution of this sensory organelle to multiple signalling pathways, little is known about how it actually mediates downstream events and why its loss causes disease states. Ciliopathies are linked to defects in either structure or function of cilia and are often associated with kidney cysts. The ciliopathy, autosomal dominant polycystic kidney disease (ADPKD), is caused by mutations to the PKD1 or PKD2 gene. The PKD gene products localize to the primary cilium, where they have been proposed to form a mechanosensory complex, sensitive to flow. Since mouse knockout models of Pkd1 or Pkd2 develop structurally normal cilia, it has been hypothesized that the loss of polycystins may lead to an impairment of flow sensing. Today, technically challenging patch clamp recordings of the primary cilium have become available, and the genetic relationship between polycystins (TRPPs) and the primary cilium has recently been dissected in detail.