Deciphering the Endothelial Shear Stress Sensor

Abstract

The single nonmotile primary cilium, protruding several microns from the apical surface, contains cytoskeletal elements in a specific fashion. It consists of 9 circularly arranged microtubule doublets, as revealed by transmission electron microscopy,1 but lacks the central ones characteristic for motile cilia and flagellae. The primary cilium is anchored to the basal body and is thereby connected to the cytoskeletal apparatus. Sorokin1 concluded that primary cilia were probably vestigial remnants of motile cilia. We now know that ciliary functions are abundant. Examples include processes involving Hedgehog and Wnt signaling2 and determining left–right asymmetry.3 Cilia functioning as sensory antennas in insect ears and the human retina are well established.4 Because of the widespread presence of primary cilia, it does not come as a surprise that many diseases, often syndromic, are caused by ciliary dysfunction. Several diseases are related to disruption of intraflagellar transport in the case of mutation in, for example, Polaris, Kif3a or various Bbs proteins that can lead to such conditions as obesity and Bardet Biedl Syndrome.5 Other cilium-related proteins involve cell membrane–bound calcium channels such as the complex formed by polycystin-1 and -2, encoded from Pkd1 and Pkd2 , respectively. Mutations cause polycystic kidney diseases.6,7 Article p 1161 Primary cilia were first described in the cardiovascular system in human embryos and adults more than 20 years ago.8 The geometry of the heart and vascular tree strongly influences hemodynamics with repercussions on the pattern of ciliation. Endothelial ciliation is restricted to areas of low and oscillatory …