Browsing by Author "Cevik, Sebiha"

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ARL13B regulates juxtaposed cilia-cilia elongation in BBSome dependent manner in Caenorhabditis elegans
(CELL PRESS, 2025) Turan, Merve Gul; Kantarci, Hanife; Cevik, Sebiha; Kaplan, Oktay I.; 0000-0002-0935-1929; 0000-0002-8733-0920; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; 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.
CiliaMiner: an integrated database for ciliopathy genes and ciliopathies
(OXFORD UNIV PRESS, 2023) Turan, Merve Gül; Orhan, Mehmet Emin; Cevik, Sebiha; Kaptan, Oktay I.; 0000-0001-5783-7168; 0000-0002-1757-1374; 0000-0002-0935-1929; 0000-0002-8733-0920; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Turan, Merve Gül; Orhan, Mehmet Emin; Cevik, Sebiha; Kaptan, 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 classifed 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-specifc clinical features, as well as subcellular localization of each protein. Additionally, the orthologs of disease genes are also provided for mice, zebrafsh, 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.
CilioGenics: an integrated method and database for predicting novel ciliary genes
(Oxford University Press, 2024) Pir, Mustafa Samet; Begar, Efe; Yenisert, Ferhan; Demirci, Hasan C.; Korkmaz, Mustafa E.; Karaman, Asli; Tsiropoulou, Sofia; Firat-Karalar, Elif Nur; Blacque, Oliver E.; Oner, Sukru S.; Doluca, Osman; Cevik, Sebiha; Kaplan, Oktay Ismail; 0000-0002-4645-7626; 0000-0002-0935-1929; 0000-0002-8733-0920; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Pir, Mustafa Samet; Yenisert, Ferhan; Demirci, Hasan C.; Korkmaz, Mustafa E.; Cevik, Sebiha; Kaplan, Oktay Ismail
Uncovering the full list of human ciliary genes holds enormous promise for the diagnosis of cilia-related human diseases, collectively known as ciliopathies. Currently, genetic diagnoses of many ciliopathies remain incomplete (1–3). While various independent approaches theoretically have the potential to reveal the entire list of ciliary genes, approximately 30% of the genes on the ciliary gene list still stand as ciliary candidates (4,5). These methods, however, have mainly relied on a single strategy to uncover ciliary candidate genes, making the categorization challenging due to variations in quality and distinct capabilities demonstrated by different methodologies. Here, we develop a method called CilioGenics that combines several methodologies (single-cell RNA sequencing, protein-protein interactions (PPIs), comparative genomics, transcription factor (TF) network analysis, and text mining) to predict the ciliary capacity of each human gene. Our combined approach provides a CilioGenics score for every human gene that represents the probability that it will become a ciliary gene. Compared to methods that rely on a single method, CilioGenics performs better in its capacity to predict ciliary genes. Our top 500 gene list includes 258 new ciliary candidates, with 31 validated experimentally by us and others. Users may explore the whole list of human genes and CilioGenics scores on the CilioGenics database (https://ciliogenics.com /).
The Joubert syndrome protein CEP41 is excluded from the distal segment of cilia in C. elegans
(2021) Sebiha Cevik; Oktay I Kaplan; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Cevik, Sebiha; Kaplan, Oktay I.
Rare diseases are a fundamental issue in today's world, affecting more than 300 million individuals worldwide. According to data from Orphanet and OMIM, about 50-60 new conditions are added to the list of over 6,000 clinically distinct diseases each year, rendering disease diagnosis and treatment even more challenging. Ciliopathies comprise a heterogeneous category of rare diseases made up of over 35 distinct diseases, including Joubert syndrome (JBTS; OMIM 213300), that are caused by functional and structural defects in cilia. JBTS is an autosomal recessive condition characterized by a range of symptoms, including cerebellar vermis hypoplasia and poor muscle tone. There are now a total of 38 genes that cause JBTS, almost all of which encode protein products that are found in cilia and cilia-associated compartments, such as the basal body and transition zone. CEP41 is a JBTS-associated protein that is found in cilia and the basal body of mammals, but its localization in other ciliary organisms remains elusive. C. elegans is an excellent model organism for studying the molecular mechanisms of rare diseases like JBTS. We, therefore, decided to use C. elegans to identify the localization of CEP41. Our microscopy analysis revealed that CEPH-41(CEntrosomal Protein Homolog 41) not only localizes to cilia but is excluded from the distal segment of the amphid and phasmid cilia in C. elegans. Furthermore, we discovered a putative X-box motif located in the promoter of ceph-41 and the expression of ceph-41 is regulated by DAF-19, a sole Regulatory Factor X (RFX) transcription factor.
Protocol for determining the average speed and frequency of kinesin and dynein-driven intraflagellar transport (IFT) in C. elegans
(Cell Press, 2022) Turan, Merve G.; Kantarci, Hanife; Temtek, Sadiye D.; Cakici, Onur; Cevik, Sebiha; Kaplan, Oktay I.; 0000-0002-0935-1929; 0000-0002-8733-0920; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Turan, Merve G.; Kantarcı, Hanife; Temtek, Sadiye D.; Çakıcı, Onur; Çevik, Sebiha; Kaplan, Oktay I.
Here, we present a protocol to image a fluorescent-labeled intraflagellar transport (IFT) component in Caenorhabditis elegans with fluorescence microscopy, including steps of sample preparations, in vivo live-cell imaging, and post-microscopy 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).
Subcellular localization of the voltage-gated K+ channel EGL-36 , a member of the KV3 subfamily, in the ciliated sensory neurons in C. elegans
(2021) Sebiha Cevik; Oktay I Kaplan; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Cevik, Sebiha; Kaplan, Oktay I.
Delineated as the first cellular organelle in 1675 by Antonie van Leeuwenhoek, cilia did not receive much attention until the 2000s, when it became apparent that cilia played a key role in the development of embryos, a variety of signaling pathways. Therefore, collective efforts by many scientists have led to the identification of many novel ciliopathy and cilia genes, while we are still far from disclosing the complete components of cilia.Here we used the ciliated sensory neurons in C. elegans as a model system that revealed the voltage-gated K+ channel EGL-36 (a member of the Shaw subfamily) as a new component associated with cilia. The confocal microscopy examination of fluorescence tagged EGL-36 together with ciliary (IFT-140) or transition zone (MKS-6) markers reveal that EGL-36 is only expressed in subsets of the ciliated sensory neurons, where it partially overlaps with the basal body signals and predominantly localizes to the periciliary membrane compartment. This expression pattern along with studies of egl-36 gain-of-function variants indicates that egl-36 is not essential for ciliogenesis in C. elegans. Our data identify the voltage-gated K+ channel EGL-36 as a new cilia-associated protein, and future studies should reveal the functional significance of EGL-36 in cilia biogenesis.
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) Cevik, Sebiha; Peng, Xiaoyu; Beyer, Tina; Pir, Mustafa Samet; Yenisert, Ferhan; Woerz, Franziska; Hoffmann, Felix; Altunkaynak, Betul; Pir, Betul; Boldt, Karsten; Karaman, Asli; Cakiroglu, Miray; Oner, S. Sadik; Cao, Ying; Ueffing, Marius; Kaplan, Oktay İsmail; 0000-0002-0935-1929; 0000-0002-6302-8997; 0000-0002-4645-7626; 0000-0002-1028-8197; 0000-0002-2693-689X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Cevik, Sebiha; Pir, Mustafa Samet; Yenisert, Ferhan; Altunkaynak, Betul; Pir, Betul; Kaplan, Oktay İsmail
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.