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The role of the cilium in normal and abnormal cell cycles: emphasis on renal cystic pathologies

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Abstract

The primary cilium protrudes from the cell surface and acts as a sensor for chemical and mechanical growth cues, with receptors for a number of growth factors (PDGFα, Hedgehog, Wnt, Notch) concentrated within the ciliary membrane. In normal tissues, the cilium assembles after cells exit mitosis and is resorbed as part of cell cycle re-entry. Although regulation of the cilium by cell cycle transitions has been appreciated for over 100 years, only recently have data emerged to indicate the cilium also exerts influence on the cell cycle. The resorption/protrusion cycle, regulated by proteins including Aurora-A, VHL, and GSK-3β, influences cell responsiveness to growth cues involving cilia-linked receptors; further, resorption liberates the ciliary basal body to differentiate into the centrosome, which performs discrete functions in S-, G2-, and M-phase. Besides these roles, the cilium provides a positional cue that regulates polarity of cell division, and thus directs cells towards fates of differentiation versus proliferation. In this review, we summarize the specific mechanisms mediating the cilia-cell cycle dialog. We then emphasize the examples of polycystic kidney disease (PKD), nephronopthisis (NPHP), and VHL-linked renal cysts as cases in which defects of ciliary function influence disease pathology, and may also condition response to treatment.

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Acknowledgments

This work was supported by National Basic Research Program (973 program) (Grant 2012CB945000) and National Natural Science Foundation of China (Grants 30830057, 30988004), and Tsinghua Research Program (to J.P.) and R01s CA63366 and CA113342 (to E.A.G.).

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  1. Protein Science Laboratory of the Ministry of Education, School of Life Sciences, Tsinghua University, Beijing, 100084, China

    Junmin Pan

  2. Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA

    Tamina Seeger-Nukpezah & Erica A. Golemis

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  1. Junmin Pan
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  2. Tamina Seeger-Nukpezah
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  3. Erica A. Golemis
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Correspondence to Junmin Pan or Erica A. Golemis.

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Pan, J., Seeger-Nukpezah, T. & Golemis, E.A. The role of the cilium in normal and abnormal cell cycles: emphasis on renal cystic pathologies. Cell. Mol. Life Sci. 70, 1849–1874 (2013). https://doi.org/10.1007/s00018-012-1052-z

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