Current situation of researches on a sensor organelle, primary cilium, to understand the pathogenesis of ciliopathy

Abstract

Primary cilium is a membrane-protruding immotile sensory organelle. It had been supposed that the cilium was a static organelle for long periods. However, recent studies have uncovered that the cilium is dynamically organized organelle in a cell cycle-dependent manner; it is formed during G 0 /G 1 phase and resorbed when the cells enter cell division cycle. Despite the primary cilium is very short and its surface area is extremely small, the cilium possesses a few kinds of G protein-coupled receptors, growth factor receptors and ion channels. Therefore, it can function as a signaling receptor for selective bioactive ligands and mechanical stresses. Dysregulation of the ciliary dynamics is linked with hereditary disorders, so called “ciliopathy”, with clinical manifestations of microcephaly, polycystic kidney, situs inversus, polydactyly, and so on. No effective medical treatment for the ciliopathies has been available. Increasing evidences about the molecular mechanisms of ciliary dynamics and ciliary functions have revealed that enormous number of molecules regulate a cycle of ciliogenesis, cilium-derived signaling, ciliary resorption and elimination. However, it is a fact that research progress is far inferior to the full disclosure of the molecular mechanisms. Further studies are required to clarify the pathogenesis of the cilipathies. Moreover, efficient medical treatments are expected to be developed by pharmacological approaches.