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Decoding cilia function. Defining specialized genes required for compartmentalized cilia biogenesis

Howard Hughes Medical Institute and Division of Biological Sciences and Department of Neurosciences, University of California at San Diego, La Jolla, CA 92093, USA.
Cell (Impact Factor: 33.12). 06/2004; 117(4):527-39.
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ABSTRACT The evolution of the ancestral eukaryotic flagellum is an example of a cellular organelle that became dispensable in some modern eukaryotes while remaining an essential motile and sensory apparatus in others. To help define the repertoire of specialized proteins needed for the formation and function of cilia, we used comparative genomics to analyze the genomes of organisms with prototypical cilia, modified cilia, or no cilia and identified approximately 200 genes that are absent in the genomes of nonciliated eukaryotes but are conserved in ciliated organisms. Importantly, over 80% of the known ancestral proteins involved in cilia function are included in this small collection. Using Drosophila as a model system, we then characterized a novel family of proteins (OSEGs: outer segment) essential for ciliogenesis. We show that osegs encode components of a specialized transport pathway unique to the cilia compartment and are related to prototypical intracellular transport proteins.

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Available from: Tomer Avidor-Reiss, Nov 12, 2014
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    • "Comparative, genome-wide analysis of flagellated and non-flagellated organisms has identified several protein datasets associated with flagella or basal bodies (Avidor-Reiss et al. 2004; Judelson et al. 2012; Li et al. 2004). Following the same strategy, we carried out a stringent reciprocal BLAST analysis by comparing CbFP sequences with the genome-encoded proteomes of eighteen selected eukaryotic species to identify putative orthologous proteins of CbFP (Supplementary Material Table S2). "
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    ABSTRACT: Flagella are conserved organelles among eukaryotes and they are composed of many proteins, which are necessary for flagellar assembly, maintenance and function. Stramenopiles, which include brown algae, diatoms and oomycetes, possess two laterally inserted flagella. The anterior flagellum (AF) extends forward and bears tripartite mastigonemes, whilst the smooth posterior flagellum (PF) often has a paraflagellar body structure. These heterogeneous flagella have served as crucial structures in algal studies especially from a viewpoint of phylogeny. However, the protein compositions of the flagella are still largely unknown. Here we report a LC-MS/MS based proteomics analysis of brown algal flagella. In total, 495 flagellar proteins were identified. Functional annotation of the proteome data revealed that brown algal flagellar proteins were associated with cell motility, signal transduction and various metabolic activities. We separately isolated AF and PF and analyzed their protein compositions. This analysis led to the identification of several AF- and PF-specific proteins. Among the PF-specific proteins, we found a candidate novel blue light receptor protein involved in phototaxis, and named it HELMCHROME because of the steering function of PF. Immunological analysis revealed that this protein was localized along the whole length of the PF and concentrated in the paraflagellar body.
    Protist 09/2014; 165(5). DOI:10.1016/j.protis.2014.07.007 · 3.56 Impact Factor
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    • "*P , 0.05; ** P , 0.01; ***P , 0.005. at least some of their cilia through compartmentalized ciliogenesis—the process in which the cilium protrudes gradually from the basal bodies located under the plasma membrane—ATK was classified as a compartment gene (Avidor-Reiss et al. 2004). However, our results show that ATK is not strictly required for cilium growth because atk mutants apparently form cilia of normal length. "
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    ABSTRACT: Sensory cilia are often encapsulated by an extracellular matrix (ECM). In Caenorhabditis elegans, Drosophila melanogaster, and vertebrates, this ECM is thought to be directly involved in ciliary mechanosensing by coupling external forces to the ciliary membrane. Drosophila mechano- and chemosensory cilia are both associated with an ECM, indicating that the ECM may have additional roles that go beyond mechanosensory cilium function. Here, we identify Artichoke (ATK), an evolutionary conserved leucine-rich repeat ECM protein that is required for normal morphogenesis and function of ciliated sensilla in Drosophila. atk is transiently expressed in accessory cells in all ciliated sensory organs during their late embryonic development. Antibody stainings show ATK protein in the ECM that surrounds sensory cilia. Loss of ATK protein in atk null mutants leads to cilium deformation and disorientation in chordotonal organs, apparently without uncoupling the cilia from the ECM, and consequently to locomotion defects. Moreover, impaired chemotaxis in atk mutant larvae suggests that, based on ATK protein localization, the ECM is also crucial for the correct assembly of chemosensory receptors. In addition to defining a novel ECM component, our findings show the importance of ECM integrity for the proper morphogenesis of ciliated organs in different sensory modalities.
    Genetics 02/2014; 196(4). DOI:10.1534/genetics.113.156323 · 4.87 Impact Factor
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    • "MBE evolutionary connection between cilia and signal transduction , in general. Unlike protostomes, vertebrates and sea urchins require cilia for effective Hh signaling (Huangfu et al. 2003; Avidor-Reiss et al. 2004; Corbit et al. 2005; Liu 2005; Rohatgi et al. 2007; Aanstad et al. 2009; Huang and Schier 2009; Rink et al. 2009; Glazer et al. 2010). Primary cilia have been linked to intercellular transduction of several developmental pathways, but the origin of these roles has been poorly understood. "
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    ABSTRACT: A relatively small number of signaling pathways govern the early patterning processes of metazoan development. The architectural changes over time to these signaling pathways offer unique insights into their evolution. In the case of Hedgehog (Hh) signaling, two very divergent mechanisms of pathway transduction have evolved. In vertebrates, signaling relies on trafficking of Hh pathway components to non-motile specialized primary cilia (Huangfu et al. 2003; Corbit et al. 2005; Liu 2005; Rohatgi, Milenkovic, and Scott 2007; Aanstad et al. 2009; Huang and Schier 2009). By contrast protostomes do not use cilia of any kind for Hh signal transduction (Avidor-Reiss et al. 2004; Rink et al. 2009; Glazer et al. 2010). How these divergent lineages adapted such dramatically different ways of activating the signaling pathway is an unanswered question. Here we present evidence that in the sea urchin, a basal deuterostome, motile cilia are required for embryonic Hh signal transduction and the Hh receptor Smoothened (Smo) localizes to cilia during active Hh signaling. This is the first evidence that Hh signaling requires motile cilia and the first case of an organism requiring cilia outside of the vertebrate lineage.
    Molecular Biology and Evolution 10/2013; DOI:10.1093/molbev/mst176 · 14.31 Impact Factor
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