Scopus İndeksli Yayınlar Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395

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Author: search.filters.author.Cevik, SebihaHas files: Yes

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  • Article
    Citation - WoS: 6
    Citation - Scopus: 6
    WDR31 Displays Functional Redundancy With GTpase-Activating Proteins (GAPs) ELMOD and RP2 in Regulating Ift Complex and Recruiting the BBsome to Cilium
    (Life Science Alliance Llc, 2023-05-19) Cevik, Sebiha; Peng, Xiaoyu; Beyer, Tina; Pir, Mustafa S.; Yenisert, Ferhan; Woerz, Franziska; Kaplan, Oktay, I
    The correct intraflagellar transport (IFT) assembly at the ciliary base and the IFT turnaround at the ciliary tip are key for the IFT to perform its function, but we still have poor understanding about how these processes are regulated. Here, we identify WDR31 as a new ciliary protein, and analysis from zebrafish and Caeno-rhabditis elegans reveals the role of WDR31 in regulating the cilia morphology. We find that loss of WDR-31 together with RP-2 and ELMD-1 (the sole ortholog ELMOD1-3) results in ciliary accumu-lations of IFT Complex B components and KIF17 kinesin, with fewer IFT/BBSome particles traveling along cilia in both anterograde and retrograde directions, suggesting that the IFT/BBSome entry into the cilia and exit from the cilia are impacted. Furthermore, anterograde IFT in the middle segment travels at increased speed in wdr-31;rpi-2;elmd-1. Remarkably, a non-ciliary protein leaks into the cilia of wdr-31;rpi-2;elmd-1, possibly because of IFT de-fects. This work reveals WDR31-RP-2-ELMD-1 as IFT and BBSome trafficking regulators.
  • Article
    Citation - WoS: 1
    Citation - Scopus: 2
    Protocol for Determining the Average Speed and Frequency of Kinesin and Dynein-Driven Intraflagellar Transport (IFT) in C. Elegans
    (Elsevier, 2022-09) Turan, Merve G.; Kantarci, Hanife; Temtek, Sadiye D.; Cakici, Onur; Cevik, Sebiha; Kaplan, Oktay, I
    Here, we present a protocol to image a fluorescent-labeled intraflagellar trans-port (IFT) component in Caenorhabditis elegans with fluorescence microscopy, including steps of sample preparations, in vivo live-cell imaging, and post -micro-scopy analysis with kymographs. This protocol breaks down all processes into three categories: (1) pre-imaging preparations, (2) preparations for the time of image acquisition, and (3) post-imaging analyses. The protocol can be applied to determine the speed and frequency of moving particles. For complete details on the use and execution of this protocol, please refer to Cevik et al. (2021).
  • Article
    Citation - WoS: 3
    Citation - Scopus: 4
    Matching Variants for Functional Characterization of Genetic Variants
    (Oxford Univ Press inc, 2023-11-02) Cevik, Sebiha; Zhao, Pei; Zorluer, Atiyye; Pir, Mustafa S.; Bian, Wenyin; Kaplan, Oktay, I
    Rapid and low-cost sequencing, as well as computer analysis, have facilitated the diagnosis of many genetic diseases, resulting in a substantial rise in the number of disease-associated genes. However, genetic diagnosis of many disorders remains problematic due to the lack of interpretation for many genetic variants, especially missenses, the infeasibility of high-throughput experiments on mammals, and the shortcomings of computational prediction technologies. Additionally, the available mutant databases are not well-utilized. Toward this end, we used Caenorhabditis elegans mutant resources to delineate the functions of eight missense variants (V444I, V517D, E610K, L732F, E817K, H873P, R1105K, and G1205E) and two stop codons (W937stop and Q1434stop), including several matching variants (MatchVar) with human in ciliopathy associated IFT-140 (also called CHE-11)//IFT140 (intraflagellar transport protein 140). Moreover, MatchVars carrying C. elegans mutants, including IFT-140(G680S) and IFT-140(P702A) for the human (G704S) (dbSNP: rs150745099) and P726A (dbSNP: rs1057518064 and a conflicting variation) were created using CRISPR/Cas9. IFT140 is a key component of IFT complex A (IFT-A), which is involved in the retrograde transport of IFT along cilia and the entrance of G protein-coupled receptors into cilia. Functional analysis of all 10 variants revealed that P702A and W937stop, but not others phenocopied the ciliary phenotypes (short cilia, IFT accumulations, mislocalization of membrane proteins, and cilia entry of nonciliary proteins) of the IFT-140 null mutant, indicating that both P702A and W937stop are phenotypic in C. elegans. Our functional data offered experimental support for interpreting human variants, by using ready-to-use mutants carrying MatchVars and generating MatchVars with CRISPR/Cas9.
  • Article
    Citation - WoS: 14
    Citation - Scopus: 14
    Ciliaminer: An Integrated Database for Ciliopathy Genes and Ciliopathies
    (Oxford Univ Press, 2023-01-01) Turan, Merve Guel; Orhan, Mehmet Emin; Cevik, Sebiha; Kaplan, Oktay, I
    Cilia are found in eukaryotic species ranging from single-celled organisms, such as Chlamydomonas reinhardtii, to humans, but not in plants. The ability to respond to repellents and/or attractants, regulate cell proliferation and differentiation and provide cellular mobility are just a few examples of how crucial cilia are to cells and organisms. Over 30 distinct rare disorders generally known as ciliopathy are caused by abnormalities or functional impairments in cilia and cilia-related compartments. Because of the complexity of ciliopathies and the rising number of ciliopathies and ciliopathy genes, a ciliopathy-oriented and up-to-date database is required. Here, we present CiliaMiner, a manually curated ciliopathy database that includes ciliopathy lists collected from articles and databases. Analysis reveals that there are 55 distinct disorders likely related to ciliopathy, with over 4000 clinical manifestations. Based on comparative symptom analysis and subcellular localization data, diseases are classified as primary, secondary or atypical ciliopathies. CiliaMiner provides easy access to all of these diseases and disease genes, as well as clinical features and gene-specific clinical features, as well as subcellular localization of each protein. Additionally, the orthologs of disease genes are also provided for mice, zebrafish, Xenopus, Drosophila, Caenorhabditis elegans and Chlamydomonas reinhardtii. CiliaMiner (https://kaplanlab.shinyapps.io/ciliaminer) aims to serve the cilia community with its comprehensive content and highly enriched interactive heatmaps, and will be continually updated.
  • Article
    Citation - WoS: 2
    Citation - Scopus: 2
    ARL13B Regulates Juxtaposed Cilia-Cilia Elongation in BBSome Dependent Manner in Caenorhabditis Elegans
    (Cell Press, 2025-02) Turan, Merve Gul; Kantarci, Hanife; Cevik, Sebiha; Kaplan, Oktay I.
    The interaction of cilia with various cellular compartments, such as axons, has emerged as a new form of cellular communication. Cilia often extend in proximity to cilia from neighboring cells. However, the mechanisms driving this process termed juxtaposed cilia-cilia elongation (JCE) remain unclear. We use fluorescence-based visualization to study the mechanisms of coordinated cilia elongation in sensory neurons of Caenorhabditis elegans. Conducting a selective gene-based screening strategy reveals that ARL-13/ARL13B and MKS-5/RPGRIP1L are essential for JCE. We demonstrate that ARL-13 modulates JCE independently of cilia length. Loss of NPHP-2/inversin along with HDAC-6 enhances the cilia misdirection phenotype of arl-13 mutants, while disruption of the BBSome complex, but not microtubule components, partially suppresses the JCE defects in arl-13 mutants. We further show changes in the phospholipid compositions in arl-13 mutants. We suggest that ARL-13 contributes to JCE, in part, through the modulation of the ciliary membrane.