Article

CP110 Suppresses Primary Cilia Formation through Its Interaction with CEP290, a Protein Deficient in Human Ciliary Disease

Department of Pathology and Cancer Institute, New York University School of Medicine, 522 1(st) Avenue, New York, NY 10016, USA.
Developmental Cell (Impact Factor: 9.71). 09/2008; 15(2):187-97. DOI: 10.1016/j.devcel.2008.07.004
Source: PubMed

ABSTRACT

Primary cilia are nonmotile organelles implicated in signaling and sensory functions. Understanding how primary cilia assemble could shed light on the many human diseases caused by mutations in ciliary proteins. The centrosomal protein CP110 is known to suppress ciliogenesis through an unknown mechanism. Here, we report that CP110 interacts with CEP290--a protein whose deficiency is implicated in human ciliary disease--in a discrete complex separable from other CP110 complexes involved in regulating the centrosome cycle. Ablation of CEP290 prevents ciliogenesis without affecting centrosome function or cell-cycle progression. Interaction with CEP290 is absolutely required for the ability of CP110 to suppress primary cilia formation. Furthermore, CEP290 and CP110 interact with Rab8a, a small GTPase required for cilia assembly. Depletion of CEP290 interferes with localization of Rab8a to centrosomes and cilia. Our results suggest that CEP290 cooperates with Rab8a to promote ciliogenesis and that this function is antagonized by CP110.

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Available from: William Y Tsang, Jan 04, 2014
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    • "However, this did not promote the growth of abnormally long centrioles, unlike depletion of CP110 and Cep97[88]suggesting that Kif24 specifically remodels centriolar microtubules without significantly altering cytoplasmic microtubules. CP110 also associates with Cep290 and Cep104[93,94]. It has been shown that CP110 restrains Cep290 from promoting the early stages of ciliogenesis in proliferating cells. "
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    DESCRIPTION: Cellular Mechanisms of Ciliary Length Control
    Full-text · Research · Jan 2016
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    • "However, this did not promote the growth of abnormally long centrioles, unlike depletion of CP110 and Cep97[88]suggesting that Kif24 specifically remodels centriolar microtubules without significantly altering cytoplasmic microtubules. CP110 also associates with Cep290 and Cep104[93,94]. It has been shown that CP110 restrains Cep290 from promoting the early stages of ciliogenesis in proliferating cells. "
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    ABSTRACT: Cilia and flagella are evolutionarily conserved, membrane-bound, microtubule-based organelles on the surface of most eukaryotic cells. They play important roles in coordinating a variety of signaling pathways during growth, development, cell mobility, and tissue homeostasis. Defects in ciliary structure or function are associated with multiple human disorders called ciliopathies. These diseases affect diverse tissues, including, but not limited to the eyes, kidneys, brain, and lungs. Many processes must be coordinated simultaneously in order to initiate ciliogenesis. These include cell cycle, vesicular trafficking, and axonemal extension. Centrioles play a central role in both cell cycle progression and ciliogenesis, making the transition between basal bodies and mitotic spindle organizers integral to both processes. The maturation of centrioles involves a functional shift from cell division toward cilium nucleation which takes place concurrently with its migration and fusion to the plasma membrane. Several proteinaceous structures of the distal appendages in mother centrioles are required for this docking process. Ciliary assembly and maintenance requires a precise balance between two indispensable processes; so called assembly and disassembly. The interplay between them determines the length of the resulting cilia. These processes require a highly conserved transport system to provide the necessary substances at the tips of the cilia and to recycle ciliary turnover products to the base using a based microtubule intraflagellar transport (IFT) system. In this review; we discuss the stages of ciliogenesis as well as mechanisms controlling the lengths of assembled cilia.
    Full-text · Article · Jan 2016
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    • "The mechanism that controls the functional change from centriole to basal body is not fully understood (Kobayashi and Dynlacht, 2011). A complex that includes CP110 and Cep97 acts as a cap at the distal end of centrioles to block mother centriole conversion to a basal body (Kleylein-Sohn et al., 2007; Spektor et al., 2007; Tsang et al., 2008). CP110 levels are regulated during the cell cycle by targeted degradation through the ubiquitin– proteasome system (D'Angiolella et al., 2010; Li et al., 2013), with TTBK2 (tau tubulin kinase 2) also being required for efficient removal of CP110 (Goetz et al., 2012; Čajánek and Nigg, 2014). "
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    ABSTRACT: Primary cilia are antenna-like sensory microtubule structures that extend from basal bodies, plasma membrane-docked mother centrioles. Cellular quiescence potentiates ciliogenesis, but the regulation of basal body formation is not fully understood. We used reverse genetics to test the role of the small calcium-binding protein, centrin2, in ciliogenesis. Primary cilia arise in most cell types but have not been described in lymphocytes. We show here that serum starvation of transformed, cultured B and T cells caused primary ciliogenesis. Efficient ciliogenesis in chicken DT40 B lymphocytes required centrin2. We disrupted CETN2 in human retinal pigmented epithelial cells, and despite having intact centrioles, they were unable to make cilia upon serum starvation, showing abnormal localization of distal appendage proteins and failing to remove the ciliation inhibitor CP110. Knockdown of CP110 rescued ciliation in CETN2-deficient cells. Thus, centrin2 regulates primary ciliogenesis through controlling CP110 levels. © 2015 Prosser and Morrison.
    Full-text · Article · Mar 2015 · The Journal of Cell Biology
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