The cell biological basis of ciliary disease

Abstract

Defects in cilia cause a broad spectrum of human diseases known collectively as the ciliopathies. Although all ciliopathies arise from defective cilia, the range of symptoms can vary significantly, and only a small subset of the possible ciliary disease symptoms may be present in any given syndrome. This complexity is puzzling until one realizes that the cilia are themselves exceedingly complex machines that perform multiple functions simultaneously, such that breaking one piece of the machine can leave some functions intact while destroying others. The clinical complexity of the ciliopathies can therefore only be understood in light of the basic cell biology of the cilia themselves, which I will discuss from the viewpoint of cell biological studies in model organisms.

Figure 1.

The anatomy of the cilium. Cilia are arrays of nine microtubule doublets that extend from the basal body (a modified centriole) and push out an extension of the plasma membrane (called the ciliary membrane). Some cilia also contain a pair of singlet microtubules in the middle called the central pair that is involved in regulating motility. Motile power is provided by two sets of dynein arms: the inner and outer arms. Motility is regulated by radial spokes that interact with the central pair. Defects in any of these structures can lead to ciliary diseases, although the precise symptoms that arise appear to depend on which structure is altered.