Cellular Mechanisms of Ciliary Length Control

Abstract

Cilia and flagella are evolutionarily conserved, membrane-bound, microtubule-based organelles on the surface of most eukaryotic cells. They play important roles in coordinating a variety of signaling pathways during growth, development, cell mobility, and tissue homeostasis. Defects in ciliary structure or function are associated with multiple human disorders called ciliopathies. These diseases affect diverse tissues, including, but not limited to the eyes, kidneys, brain, and lungs. Many processes must be coordinated simultaneously in order to initiate ciliogenesis. These include cell cycle, vesicular trafficking, and axonemal extension. Centrioles play a central role in both cell cycle progression and ciliogenesis, making the transition between basal bodies and mitotic spindle organizers integral to both processes. The maturation of centrioles involves a functional shift from cell division toward cilium nucleation which takes place concurrently with its migration and fusion to the plasma membrane. Several proteinaceous structures of the distal appendages in mother centrioles are required for this docking process. Ciliary assembly and maintenance requires a precise balance between two indispensable processes; so called assembly and disassembly. The interplay between them determines the length of the resulting cilia. These processes require a highly conserved transport system to provide the necessary substances at the tips of the cilia and to recycle ciliary turnover products to the base using a based microtubule intraflagellar transport (IFT) system. In this review; we discuss the stages of ciliogenesis as well as mechanisms controlling the lengths of assembled cilia.

Keywords: Ciliogenesis; IFT; basal body; cell cycle; centrioles; ciliary vesicles.

Figure 1

A schematic of basal body docking and ciliogenesis. As the mother centriole begins its differentiation and migration to the cell surface it acquires distal appendenges and distal appendage vesicles (DAV) from the golgi. Proteins such as EHD1 in conjunction with Rab8 help to expand the DAV into a ciliary vesicle (CV). As ciliogenesis continues the basal body acquires positive regulators of ciliogenesis and removes negative regulators such as Trichoplein, allowing docking and the formation of the transition zone (TZ). Once the basal body docks at the plasma membrane (PM) axonemal extension can take place into the extra-cellular space.

Figure 2

An illustration of molecular mechanisms of primary cilia disassembly (along the side) in mammalian cells and possible ciliary length control mechanisms (lower portion).