Do cilia put brakes on the cell cycle?

Genentech Inc, 1 DNA way, MC214, South San Francisco, California 94080, USA.
Nature Cell Biology (Impact Factor: 19.68). 04/2011; 13(4):340-2. DOI: 10.1038/ncb0411-340
Source: PubMed


Two papers in this issue show that dynein-binding proteins may regulate the G1-S transition through an effect on cilia. Nde1, a known partner of dynein light chain LC8, controls ciliary length in vitro and in zebrafish, and influences the G1-S progression. The phosphorylation of Tctex1, a dynein light chain, modulates cilia length and accelerates G1-S, thereby regulating proliferation-differentiation decisions in the developing mouse neocortex.

13 Reads
  • Source
    • "The cilium projects from the basal body, which originates from the active mother centriole. Because of these structural roots, the primary cilium is expected to be involved in the regulation of progression into the cell cycle (Tucker et al., 1979;Pan and Snell, 2007;Pugacheva et al., 2007;Plotnikova et al., 2008;Plotnikova et al., 2009;Jackson, 2011;Goto et al., 2013). Additionally, evidence for the primary cilium's role in regulating the cell cycle has been published describing the localization of several critical cell cycle proteins to the cilium, including Aurora A, which functions in deciliation and prevention of cilium regeneration (Pugacheva et al., 2007;Inoko et al., 2012;Goto et al., 2013). "
    [Show abstract] [Hide abstract]
    ABSTRACT: For many years now, researchers have known of a sensory appendage on the surface of most differentiated cell types, called primary cilium. Primary cilia are both chemo-and mechano-sensory in function and have an obvious role in cell cycle control. Because of this, it has been thought that primary cilia are not found on rapidly proliferating cells, as e.g. cancer cells. Here we report using immunofluorescent staining for the ciliary protein Arl13b that primary cilia are frequently found on HeLa (human epithelial adenocarcinoma) and other cancer cell lines such as MG63 (human osteosarcoma) commonly used for cell culture studies, and that the ciliated population is significantly higher (ave. 28.6% and 46.5%, respectively in starved and 15.7 to 18.6% in un-starved cells) than previously anticipated. Our finding impacts the current perception of primary cilia formed in highly proliferative cells. This article is protected by copyright. All rights reserved.
    Full-text · Article · Jun 2015 · Cell Biology International
  • Source
    • "In mammalian cells, distal ciliary resorption is required for proper G1-S transition (Kim et al., 2011; Li et al., 2011), but complete resorption is not necessary (Kim et al., 2011; Spalluto et al., 2013). One speculation is that the first phase resorption may generate signals for S phase entry, and once the cell acquires the capacity to enter S phase, the second phase shortening would proceed, leading to disassembly of the proximal portion of cilia to release the basal body (centriole) for spindle formation during mitosis (Jackson, 2011; Pan and Snell, 2007). In support of this hypothesis, we have found that CALK and CrKin13 phosphorylation can be induced by the flagellarshortening process during the first shortening phase. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cilia and flagella are dynamic organelles that undergo assembly and disassembly during each cell cycle. They are structurally polarized, and the mechanisms by which these organelles are disassembled are incompletely understood. Here, we show that flagellar resorption occurs in two distinct phases of length-dependent regulation. A CDK-like kinase, encoded by flagellar shortening 1 (FLS1), is required for the normal rate of disassembly of only the distal part of the flagellum. Mechanistically, loss of function of FLS1 prevents the initial phosphorylation of CALK, an aurora-like kinase that regulates flagellar shortening, and induces the earlier onset of the inhibitory phosphorylation of CrKinesin13, a microtubule depolymerase, which is involved in flagellar shortening. In addition, CALK and CrKinesin13 phosphorylation can also be induced by the process of flagellar shortening itself, demonstrating an example of cilia-generated signaling not requiring the binding of a ligand or the stimulation of an ion channel. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · Mar 2015 · Cell Reports
  • Source
    • "This relationship implies that ciliogenesis and cell proliferation may be mutually exclusive processes, but it remains controversial whether or not (de)ciliation affects cell cycle progression [30, 31, 35–37]. However, several recent publications provide some clues [47–49, 74]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In most cell types, primary cilia protrude from the cell surface and act as major hubs for cell signaling, cell differentiation, and cell polarity. With the exception of some cells ciliated during cell proliferation, most cells begin to disassemble their primary cilia at cell cycle re-entry. Although the role of primary cilia disassembly on cell cycle progression is still under debate, recent data have emerged to support the idea that primary cilia exert influence on cell cycle progression. In this review, we emphasize a non-mitotic role of Aurora-A not only in the ciliary resorption at cell cycle re-entry but also in continuous suppression of cilia regeneration during cell proliferation. We also summarize recent new findings indicating that forced induction/suppression of primary cilia can affect cell cycle progression, in particular the transition from G0/G1 to S phase. In addition, we speculate how (de)ciliation affects cell cycle progression.
    Full-text · Article · Mar 2013 · Cellular and Molecular Life Sciences CMLS
Show more