Cilium Assembly

Stable Identifier
R-HSA-5617833
Type
Pathway
Species
Homo sapiens
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Cilia are membrane covered organelles that extend from the surface of eukaryotic cells. Cilia may be motile, such as respiratory cilia) or non-motile (such as the primary cilium) and are distinguished by the structure of their microtubule-based axonemes. The axoneme consists of nine peripheral doublet microtubules, and in the case of many motile cilia, may also contain a pair of central single microtubules. These are referred to as 9+0 or 9+2 axonemes, respectively. Relative to their non-motile counterparts, motile cilia also contain additional structures that contribute to motion, including inner and outer dynein arms, radial spokes and nexin links. Four main types of cilia have been identified in humans: 9+2 motile (such as respiratory cilia), 9+0 motile (nodal cilia), 9+2 non-motile (kinocilium of hair cells) and 9+0 non-motile (primary cilium and photoreceptor cells) (reviewed in Fliegauf et al, 2007). This pathway describes cilia formation, with an emphasis on the primary cilium. The primary cilium is a sensory organelle that is required for the transduction of numerous external signals such as growth factors, hormones and morphogens, and an intact primary cilium is needed for signaling pathways mediated by Hh, WNT, calcium, G-protein coupled receptors and receptor tyrosine kinases, among others (reviewed in Goetz and Anderson, 2010; Berbari et al, 2009; Nachury, 2014). Unlike the motile cilia, which are generally present in large numbers on epithelial cells and are responsible for sensory function as well as wave-like beating motions, the primary cilium is a non-motile sensory organelle that is present in a single copy at the apical surface of most quiescent cells (reviewed in Hsiao et al, 2012). Cilium biogenesis involves the anchoring of the basal body, a centriole-derived organelle, near the plasma membrane and the subsequent polymerization of the microtubule-based axoneme and extension of the plasma membrane (reviewed in Ishikawa and Marshall, 2011; Reiter et al, 2012). Although the ciliary membrane is continuous with the plasma membrane, the protein and lipid content of the cilium and the ciliary membrane are distinct from those of the bulk cytoplasm and plasma membrane (reviewed in Emmer et al, 2010; Rohatgi and Snell, 2010). This specialized compartment is established and maintained during cilium biogenesis by the formation of a ciliary transition zone, a proteinaceous structure that, with the transition fibres, anchors the basal body to the plasma membrane and acts as a ciliary pore to limit free diffusion from the cytosol to the cilium (reviewed in Nachury et al, 2010; Reiter et al, 2012). Ciliary components are targeted from the secretory system to the ciliary base and subsequently transported to the ciliary tip, where extension of the axoneme occurs, by a motor-driven process called intraflagellar transport (IFT). Anterograde transport of cargo from the ciliary base to the tip of the cilium requires kinesin-2 type motors, while the dynein-2 motor is required for retrograde transport back to the ciliary base. In addition, both anterograde and retrograde transport depend on the IFT complex, a multiprotein assembly consisting of two subcomplexes, IFT A and IFT B. The primary cilium is a dynamic structure that undergoes continuous steady-state turnover of tubulin at the tip; as a consequence, the IFT machinery is required for cilium maintenance as well as biogenesis (reviewed in Bhogaraju et al, 2013; Hsiao et al, 2012; Li et al, 2012; Taschner et al, 2012; Sung and Leroux, 2013). The importance of the cilium in signaling and cell biology is highlighted by the wide range of defects and disorders, collectively known as ciliopathies, that arise as the result of mutations in genes encoding components of the ciliary machinery (reviewed in Goetz and Anderson, 2010; Madhivanan and Aguilar, 2014).

Literature References
PubMed ID Title Journal Year
22653444 The base of the cilium: roles for transition fibres and the transition zone in ciliary formation, maintenance and compartmentalization

Reiter, JF, Blacque, OE, Leroux, MR

EMBO Rep. 2012
21427764 Ciliogenesis: building the cell's antenna

Ishikawa, H, Marshall, WF

Nat. Rev. Mol. Cell Biol. 2011
20399632 The ciliary membrane

Rohatgi, R, Snell, WJ

Curr. Opin. Cell Biol. 2010
22389062 The emerging role of Arf/Arl small GTPases in cilia and ciliopathies

Li, Y, Ling, K, Hu, J

J. Cell. Biochem. 2012
23945166 Intraflagellar transport complex structure and cargo interactions

Bhogaraju, S, Engel, BD, Lorentzen, E

Cilia 2013
20145001 Molecular mechanisms of protein and lipid targeting to ciliary membranes

Emmer, BT, Maric, D, Engman, DM

J. Cell. Sci. 2010
23351793 Trafficking in and to the primary cilium

Hsiao, YC, Tuz, K, Ferland, RJ

Cilia 2012
25047619 How do cilia organize signalling cascades?

Nachury, MV

Philos. Trans. R. Soc. Lond., B, Biol. Sci. 2014
25040720 Ciliopathies: the trafficking connection

Madhivanan, K, Aguilar, RC

Traffic 2014
24296415 The roles of evolutionarily conserved functional modules in cilia-related trafficking

Sung, CH, Leroux, MR

Nat. Cell Biol. 2013
17955020 When cilia go bad: cilia defects and ciliopathies

Fliegauf, M, Benzing, T, Omran, H

Nat. Rev. Mol. Cell Biol. 2007
19575670 Trafficking to the ciliary membrane: how to get across the periciliary diffusion barrier?

Nachury, MV, Seeley, ES, Jin, H

Annu. Rev. Cell Dev. Biol. 2010
19602418 The primary cilium as a complex signaling center

Berbari, NF, O'Connor, AK, Haycraft, CJ, Yoder, BK

Curr. Biol. 2009
20395968 The primary cilium: a signalling centre during vertebrate development

Goetz, SC, Anderson, KV

Nat. Rev. Genet. 2010
22118932 Architecture and function of IFT complex proteins in ciliogenesis

Taschner, M, Bhogaraju, S, Lorentzen, E

Differentiation 2012
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