Ciliogenesis: building the cell’s antenna. Nat Rev Mol Cell Biol

Department of Biochemistry and Biophysics, University of California, San Francisco, BOX 2200 GH-N372F, 600 16th Street, San Francisco, California 94158, USA.
Nature Reviews Molecular Cell Biology (Impact Factor: 37.81). 04/2011; 12(4):222-34. DOI: 10.1038/nrm3085
Source: PubMed


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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    • "The docked mother centriole elongates and the axonemal extension follows. Finally, cilium assembly and maintenance are achieved by intraflagellar transport (IFT) mediated by the concerted action of anterograde kinesins (IFT-B complex) and retrograde dynein (IFT-A complex) (Ishikawa & Marshall, 2011; Kobayashi & Dynlacht, 2011; Nigg & Stearns, 2011; Sung & Leroux, 2013). Three negative regulators of ciliogenesis have been shown to be destructed or removed from ciliary structures at the onset of ciliogenesis. "

    The EMBO Journal 07/2015; DOI:10.15252/embj.201490831 · 10.43 Impact Factor
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    • "The primary cilium is a microtubule (MT)-based, nonmotile projection located on the surface of most vertebrate cells that senses extracellular information to transduce signals required for cell proliferation, embryogenesis, and tissue homeostasis (Ishikawa and Marshall, 2011). Dysfunctions of primary cilia cause ciliopathies characterized by a range of clinical symptoms including polycystic kidney, obesity, neuronal, and other developmental abnormalities (Nigg and Raff, 2009). "
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    ABSTRACT: The primary cilium is an antenna-like, microtubule-based organelle on the surface of most vertebrate cells for receiving extracellular information. Although primary cilia form in the quiescent phase, ciliary disassembly occurs when quiescent cells re-enter the proliferative phase. It was shown that a mitotic kinase, Polo-like kinase 1 (PLK1), is required for cell-proliferation-coupled primary cilia disassembly. Here, we report that kinesin superfamily protein 2A (KIF2A), phosphorylated at T554 by PLK1, exhibits microtubule-depolymerizing activity at the mother centriole to disassemble the primary cilium in a growth-signal-dependent manner. KIF2A-deficient hTERT-RPE1 cells showed the impairment of primary cilia disassembly following growth stimulation. It was also found that the PLK1-KIF2A pathway is constitutively active in cells from patients with premature chromatid separation (PCS) syndrome and is responsible for defective ciliogenesis in this syndrome. These findings provide insights into the roles of the PLK1-KIF2A pathway in physiological cilia disassembly and cilia-associated disorders. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 02/2015; 341(5). DOI:10.1016/j.celrep.2015.01.003 · 8.36 Impact Factor
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    • "CEP83 is specifically required for centriole-to-membrane docking (Joo et al. 2013; Tanos et al. 2013). The subsequent elongation of the ciliary axoneme depends on intraflagellar transport (IFT), a microtubule motor-based delivery system that transports cargos from outside the cilia to the growing tip, or retrieves them to the cell body (reviewed by Pedersen and Rosenbaum 2008; Ishikawa and Marshall 2011; Avasthi and Marshall 2012). Ciliogenesis first requires the removal of CP110 and Cep97 from the distal end of the centriole (Fig. 7). "
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    ABSTRACT: The centrosome was discovered in the late 19th century when mitosis was first described. Long recognized as a key organelle of the spindle pole, its core component, the centriole, was realized more than 50 or so years later also to comprise the basal body of the cilium. Here, we chart the more recent acquisition of a molecular understanding of centrosome structure and function. The strategies for gaining such knowledge were quickly developed in the yeasts to decipher the structure and function of their distinctive spindle pole bodies. Only within the past decade have studies with model eukaryotes and cultured cells brought a similar degree of sophistication to our understanding of the centrosome duplication cycle and the multiple roles of this organelle and its component parts in cell division and signaling. Now as we begin to understand these functions in the context of development, the way is being opened up for studies of the roles of centrosomes in human disease. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.
    Cold Spring Harbor Perspectives in Medicine 02/2015; 7(1-2). DOI:10.1101/cshperspect.a015800 · 9.47 Impact Factor
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