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.

Intraflagellar transport: mechanisms of motor action, cooperation, and cargo delivery

“…It has long been recognized that IFT is required for ciliogenesis because it delivers cargo consisting of axonemal precursors such as tubulin subunits, preassembled radial‐spoke complexes and dynein arms to their site of assembly at the tip of the cilium . The delivery of these same cargo molecules is also relevant to the interesting topic of cilium length control, a topic that has been pioneered by Marshall and others . IFT is also thought to be involved in the delivery of specific molecules required for the compartmentalization of the cilium and, via cooperation with the BBSome, to contribute to the biogenesis of the ciliary membrane .…”

To beat, or not to beat, that is question! The spectrum of ciliopathies

“…Historically, cilia were classified into two main groups: motile “9 + 2” cilia; multiple cilia, and non‐motile (also called sensory, or primary) “9 + 0” cilia; monocilia on the cell surface . This initial classification is too simplistic with the discovery of overlapping features of both motile and non‐motile cilia .…”

“…What is also apparent is that for different classes of motile cilia each have a distinct beat pattern. Motile “9 + 0” nodal monocilia move in a clockwise rotatory motion, in contrast, the sperm flagellum (“9 + 2” monocilium) produces a sigmoidal three‐dimensional beat pattern (Figure ) . Cilia found in the respiratory tract and cilia found on the ependymal surface of the brain ventricles have a “9 + 2” structure.…”

“…2,4,6,33,34 Historically, cilia were classified into two main groups: motile "9 + 2" cilia; multiple cilia, and non-motile (also called sensory, or primary) "9 + 0" cilia; monocilia on the cell surface. 2,4,9,32,35 This initial classification is too simplistic with the discovery of overlapping features of both motile and non-motile cilia. 2,15,32 In addition, highly specialized cilia have been described, with specific ultrastructural and functional features.…”

The Biology of Ciliary Dynamics

“…We will not discuss deciliation (or deflagellation), that is, cilium detachment from cell body through severing the axoneme distal to the ciliary transition zone. Several comprehensive reviews have also covered the signaling pathways and components key to ciliary disassembly, and its connection to cancer (Plotnikova et al 2008; Izawa et al 2015; Keeling et al 2016; Liang et al 2016). In this review, we will focus on discussing the biological importance of ciliary dynamics during development, differentiation, homeostasis, and diseases.…”