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Ciliogenesis: building the cell's antenna

Key Points

  • Cilia are complex sensory and motile organelles found on almost all cells of the body. The complexity of the cilium raises the question of how it is built in an orderly fashion.

  • Ciliary assembly proceeds in a stepwise manner: centrioles form basal bodies, dock on the cortex and induce outgrowth of the cilium. Assembly also involves protein-trafficking from the cytoplasm to the base of the cilium and selective import of ciliary proteins through a channel that may be analogous to the nuclear pore complex.

  • Sustained growth of cilia requires active transport, which is provided by the intraflagellar transport (IFT) system.

  • Assembly of cilia is a function of cell cycle stage and is tightly regulated to control the length of the final structure.

  • Ciliary length seems to result from a continuous steady-state balance of assembly and disassembly, with the inherent length-dependence of IFT-mediated transport leading to a length-dependent assembly rate.

Abstract

The cilium is a complex organelle, the assembly of which requires the coordination of motor-driven intraflagellar transport (IFT), membrane trafficking and selective import of cilium-specific proteins through a barrier at the ciliary transition zone. Recent findings provide insights into how cilia assemble and disassemble in synchrony with the cell cycle and how the balance of ciliary assembly and disassembly determines the steady-state ciliary length, with the inherent length-dependence of IFT rendering the ciliary assembly rate a decreasing function of length. As cilia are important in sensing and processing developmental signals and directing the flow of fluids such as mucus, defects in ciliogenesis and length control are likely to underlie a range of cilium-related human diseases.

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Figure 1: The architecture of cilia.
Figure 2: Intraflagellar transport machinery.
Figure 3: Ciliary trafficking pathways.
Figure 4: Synchronization of ciliary assembly and disassembly with the cell cycle.
Figure 5: Ciliary length-control mechanisms.

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Acknowledgements

We thank B. Engel and members of the Marshall laboratory for helpful discussions and editorial comments. We also thank S. Nonaka for providing the nodal cilia picture. We apologize to those authors whose work we could not cite owing to space limitations. This work was supported by the US National Institutes of Health and the W. M. Keck Foundation.

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Glossary

Leftward flow

Flow of extraembryonic fluid across the node surface that moves to the left side of the animal.

Node

The anterior end of the primitive streak. Leftward flow in the node is important to determine the left–right axis of the body.

Axoneme

The insoluble microtubule-based structural scaffold of a cilium.

Basal body

A centriole that is acting to nucleate a cilium.

B tubule

The incomplete second microtubule that, together with the A tubule, forms the outer doublet of the ciliary axoneme.

Primary cilium

A cilium, the basal body of which is the mother centriole that the cell inherited during the previous mitosis. The term is meant to contrast with 'secondary cilia', which refers to any other cilia that form later in the cell cycle.

Centriole

A cylindrical array of nine microtubule triplets that is found in the core of the centrosome.

Polyglutamylation

Modification by addition of multiple glutamate residues onto a protein.

Bardet–Biedl syndrome

A ciliopathy that is characterized by obesity, retinitis pigmentosa, polydactyly and cognitive disability.

Endocytosis

The pathway by which cells take up molecules from the plasma membrane by forming invaginations that close off to become intracellular vesicles.

Guanine nucleotide exchange factor

A protein that stimulates exchange of GDP for GTP on GTP-binding proteins, including G-proteins and GTPases.

Ciliary waveform

A type of ciliary motility that is characterized by large asymmetrical bending motions, as opposed to the flagellar waveform which is characterized by a symmetrical sine-wave-like bending pattern.

Nephronophthisis

A paediatric kidney cyst disease that is characterized by normal-sized kidneys with abnormally dilated ducts.

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Ishikawa, H., Marshall, W. Ciliogenesis: building the cell's antenna. Nat Rev Mol Cell Biol 12, 222–234 (2011). https://doi.org/10.1038/nrm3085

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