Assembling a primary cilium

Abstract

Cilia are evolutionarily conserved, membrane-bound, microtubular projections emanating from the cell surface. They are assembled on virtually all cell types in the human body, with very few exceptions, and several recent reviews have covered the topic in great detail. The cilium is assembled from mature (mother) centrioles or basal bodies, which serve to nucleate growth of axonemes that give rise to two structurally distinct variants, motile and nonmotile cilia. Whereas motile cilia are typically found in large bundles and beat synchronously to generate fluid flow, primary cilia (with the exception of those found at the embryonic node) are generally immotile and are found as solitary organelles. Remarkably, until recently, the primary cilium was considered a vestigial organelle without apparent biological function. However, research over the past decade has established that the primary cilium is capable of transducing essential signaling information from the extracellular milieu. Defects in the cilium, and the structure from which it arises, the basal body, have been shown to cause a spectrum of diseases, ranging from developmental defects to obesity, diabetes, and cancer. Many of these diseases, or ciliopathies, are manifested as genetic syndromes, such as Joubert syndrome, Bardet-Biedel (BBS), Meckel-Gruber (MKS), and Nephronophthisis (NPHP), illustrating the importance of understanding cilium structure and function and the mechanisms required for its assembly. This review focuses primarily on recent advances in our understanding of the regulatory controls governing the assembly and maintenance of the primary cilium.

Figure 1

Summary of factors that regulate the assembly or disassembly of cilia. Upon cilia formation and elongation (red arrow), IFT components, MARK4, and TTBK2 are recruited to the basal body, whereas ciliary inhibitors, such as CP110, Cep97, Kif24, and Trichoplein are displaced. Ciliary elongation is directly promoted by the abundance and motility rate of the IFT-B complex and the availability of soluble tubulin as axonemal precursors. Several structural modifications also occur during cilia formation; the distal and sub-distal appendages become transition fibers and basal feet, respectively, and the formation of transition zones and ciliary pockets for their role in ciliary trafficking. Conversely, during ciliary disassembly (black arrow), CP110, Cep97, Kif24, and Trichoplein are expressed at the basal body. Additionally, several factors, including components involved in the IFT-A complex, axonemal deacetylation, axonemal microtubule depolymerization, and actin polymerization negatively regulate cilium assembly.