Researcher:
Odabaşı, Ezgi

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Ezgi

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Odabaşı

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Odabaşı, Ezgi

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2016 - 201932020 - 20235

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    First person
    (The Company of Biologists, 2023) Odabaşı, Ezgi; Other; N/A
    First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Ezgi Odabasi is first author on "CCDC 66 regulates primary cilium length and signaling via interactions with transition zone and axonemal proteins', published in JCS. Ezgi is a postdoc in the lab of Elif Nur Firat-Karalar at Koc University, Istanbul, Turkey, investigating regulation of centrosome or cilium complex by centriolar satellites.
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    CCDC66 regulates primary cilium length and signaling via interactions with transition zone and axonemal proteins
    (The Company of Biologists, 2023) Frikstad, Kari-Anne M.; Patzke, Sebastian; Department of Molecular Biology and Genetics; Odabaşı, Ezgi; Çonkar, Deniz; Deretic, Jovana; Batman, Umut; Karalar, Elif Nur Fırat; Other; Researcher; Researcher; Master Student; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences; N/A; N/A; N/A; N/A; 206349
    The primary cilium is a microtubule-based organelle that serves as a hub for many signaling pathways. It functions as part of the centrosome or cilium complex, which also contains the basal body and the centriolar satellites. Little is known about the mechanisms by which the microtubule-based ciliary axoneme is assembled with a proper length and structure, particularly in terms of the activity of microtubule-associated proteins (MAPs) and the crosstalk between the different compartments of the centrosome or cilium complex. Here, we analyzed CCDC66, a MAP implicated in cilium biogenesis and ciliopathies. Live-cell imaging revealed that CCDC66 compartmentalizes between centrosomes, centriolar satellites, and the ciliary axoneme and tip during cilium biogenesis. CCDC66 depletion in human cells causes defects in cilium assembly, length and morphology. Notably, CCDC66 interacts with the ciliopathy-linked MAPs CEP104 and CSPP1, and regulates axonemal length and Hedgehog pathway activation. Moreover, CCDC66 is required for the basal body recruitment of transition zone proteins and intraflagellar transport B (IFT-B) machinery. Overall, our results establish CCDC66 as a multifaceted regulator of the primary cilium and provide insight into how ciliary MAPs and subcompartments cooperate to ensure assembly of functional cilia.
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    Unraveling the mysteries of centriolar satellites: time to rewrite the textbooks about the centrosome/cilium complex
    (American Society for Cell Biology, 2020) N/A; Department of Molecular Biology and Genetics; Department of Molecular Biology and Genetics; N/A; Odabaşı, Ezgi; Karalar, Elif Nur Fırat; Batman, Umut; Other; Faculty Member; Master Student; Department of Molecular Biology and Genetics; College of Sciences; College of Sciences; Graduate School of Sciences and Engineering; N/A; 206349; N/A
    Centriolar satellites are membraneless granules that localize and move around centrosomes and cilia. Once referred to as structures with no obvious function, research in the past decade has identified satellites as key regulators of a wide range of cellular and organismal processes. Importantly, these studies have revealed a substantial overlap between functions, proteomes, and disease links of satellites with centrosomes and cilia. Therefore, satellites are now accepted as the “third component” of the vertebrate centrosome/cilium complex, which profoundly changes the way we think about the assembly, maintenance, and remodeling of the complex at the cellular and organismal levels. In this perspective, we first provide an overview of the cellular and structural complexities of centriolar satellites. We then describe the progress in the identification of the satellite interactome, which have paved the way to a molecular understanding of their mechanism of action and assembly mechanisms. After exploring current insights into their functions as recently described by loss-of-function studies and comparative evolutionary approaches, we discuss major unanswered questions regarding their functional and compositional diversity and their functions outside centrosomes and cilia.
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    The centriolar satellite protein Cep109 and Cep290 interact and are required for recruitment of BBS proteins to the cilium
    (Amer Soc Cell Biology, 2016) Rauniyar, N.; Yates, J., I. I. I.; N/A; N/A; N/A; Department of Molecular Biology and Genetics; Çonkar, Deniz; Culfa, Efraim; Odabaşı, Ezgi; Karalar, Elif Nur Fırat; Phd Student; Master Student; Other; Faculty Member; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; N/A; N/A; College of Sciences; N/A; N/A; N/A; 206349
    Defects in centrosome and cilium function are associated with phenotypically related syndromes called ciliopathies. Centriolar satellites are centrosome-associated structures, defined by the protein PCM1, that are implicated in centrosomal protein trafficking. We identify Cep72 as a PCM1-interacting protein required for recruitment of the ciliopathy-associated protein Cep290 to centriolar satellites. Loss of centriolar satellites by depletion of PCM1 causes relocalization of Cep72 and Cep290 from satellites to the centrosome, suggesting that their association with centriolar satellites normally restricts their centrosomal localization. We identify interactions between PCM1, Cep72, and Cep290 and find that disruption of centriolar satellites by overexpression of Cep72 results in specific aggregation of these proteins and the BBSome component BBS4. During ciliogenesis, BBS4 relocalizes from centriolar satellites to the primary cilium. This relocalization occurs normally in the absence of centriolar satellites (PCM1 depletion) but is impaired by depletion of Cep290 or Cep72, resulting in defective ciliary recruitment of the BBSome subunit BBS8. We propose that Cep290 and Cep72 in centriolar satellites regulate the ciliary localization of BBS4, which in turn affects assembly and recruitment of the BBSome. Finally, we show that loss of centriolar satellites in zebrafish leads to phenotypes consistent with cilium dysfunction and analogous to those observed in human ciliopathies.
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    Oncogenic K-Ras4B dimerization enhances downstream mitogen-activated protein kinase signaling
    (Academic Press Ltd- Elsevier Science Ltd, 2020) Jang, Hyunbum; Tsai, Chung-Jung; Nussinov, Ruth; N/A; N/A; N/A; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; N/A; Department of Chemical and Biological Engineering; Muratçıoğlu, Serena; Aydın, Cihan; Odabaşı, Ezgi; Karalar, Elif Nur Fırat; Kavaklı, İbrahim Halil; Özdemir, E. Sıla; Keskin, Özlem; Gürsoy, Attila; PhD Student; Researcher; Other; Faculty Member; Faculty Member; PhD Student; Faculty Member; Faculty Member; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; N/A; N/A; College of Sciences; College of Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; Department of Computer Engineering; N/A; 214696; 26605; 8745; 206349; 40319; 26605; 8745
    Ras recruits and activates effectors that transmit receptor-initiated signals. Monomeric Ras can bind Raf; however, Raf's activation requires dimerization, which can be facilitated by Ras dimerization. Previously, we showed that active K-Ras4B dimerizes in silico and in vitro through two major interfaces: (i) beta-interface, mapped to Switch I and effector-binding regions, (ii) alpha-interface at the allosteric lobe. Here, we chose constitutively active K-Ras4B as our control and two double mutants (K101D and R102E; and R41E and K42D) in the alpha- and beta-interfaces. Two of the mutations are from The Cancer Genome Atlas (TCGA) and the Catalogue of Somatic Mutations In Cancer (COSMIC) data sets. R41 and R102 are found in several adenocarcinomas in Ras isoforms. We performed site-directed mutagenesis, cellular localization experiments, and molecular dynamics (MD) simulations to assess the impact of the mutations on K-Ras4B dimerization and function. alpha-interface K101D/R102E double mutations reduced dimerization but only slightly reduced downstream phosphorylated extracellular signal-regulated kinase (ERK) (pERK) levels. While beta-interface R41E/K42D double mutations did not interfere with dimerization, they almost completely blocked KRas4B-mediated ERK phosphorylation. Both double mutations increased downstream phosphorylated Akt (pAkt) levels in cells. Changes in pERK and pAkt levels altered ERK- and Akt-regulated gene expressions, such as EGR1, JUN, and BCL2L11. These results underscore the role of the alpha-interface in K-Ras4B homodimerization and the beta-surface in effector binding. MD simulations highlight that the membrane and hypervariable region (HVR) interact with both alpha- and beta-interfaces of K-Ras4B mutants, respectively, inhibiting homodimerization and probably effector binding. Mutations at both interfaces interfered with mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase signaling but in different forms and extents. We conclude that dimerization is not necessary but enhances downstream MAPK signaling.
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    PublicationOpen Access
    Unraveling the mysteries of centriolar satellites: time to rewrite the textbooks about the centrosome/cilium complex
    (The American Society for Cell Biology, 2020) Department of Molecular Biology and Genetics; Karalar, Elif Nur Fırat; Odabaşı, Ezgi; Batman, Umut; Other; Department of Molecular Biology and Genetics; College of Sciences; Graduate School of Sciences and Engineering; 206349; N/A; N/A
    Centriolar satellites are membraneless granules that localize and move around centrosomes and cilia. Once referred to as structures with no obvious function, research in the past decade has identified satellites as key regulators of a wide range of cellular and organismal processes. Importantly, these studies have revealed a substantial overlap between functions, proteomes, and disease links of satellites with centrosomes and cilia. Therefore, satellites are now accepted as the ""third component"" of the vertebrate centrosome/cilium complex, which profoundly changes the way we think about the assembly, maintenance, and remodeling of the complex at the cellular and organismal levels. In this perspective, we first provide an overview of the cellular and structural complexities of centriolar satellites. We then describe the progress in the identification of the satellite interactome, which have paved the way to a molecular understanding of their mechanism of action and assembly mechanisms. After exploring current insights into their functions as recently described by loss-of-function studies and comparative evolutionary approaches, we discuss major unanswered questions regarding their functional and compositional diversity and their functions outside centrosomes and cilia.
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    PublicationOpen Access
    The centriolar satellite protein CCDC66 interacts with CEP290 and functions in cilium formation and trafficking
    (The Company of Biologists (United Kingdom), 2017) Rauniyar, Navin; Yates, John R., III; Department of Molecular Biology and Genetics; Karalar, Elif Nur Fırat; Çonkar, Deniz; Culfa, Efraim; Odabaşı, Ezgi; PhD Student; Master Student; Other; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; 206349; N/A; N/A; N/A
    Centriolar satellites are membrane-less structures that localize and move around the centrosome and cilium complex in a microtubule-dependent manner. They play important roles in centrosome- and cilium-related processes, including protein trafficking to the centrosome and cilium complex, and ciliogenesis, and they are implicated in ciliopathies. Despite the important regulatory roles of centriolar satellites in the assembly and function of the centrosome and cilium complex, the molecular mechanisms of their functions remain poorly understood. To dissect the mechanism for their regulatory roles during ciliogenesis, we performed an analysis to determine the proteins that localize in close proximity to the satellite protein CEP72, among which was the retinal degeneration gene product CCDC66. We identified CCDC66 as a microtubule-associated protein that dynamically localizes to the centrosome, centriolar satellites and the primary cilium throughout the cell cycle. Like the bbsome component BBS4, CCDC66 distributes between satellites and the primary cilium during ciliogenesis. CCDC66 has extensive proximity interactions with centrosome and centriolar satellite proteins, and co-immunoprecipitation experiments revealed interactions between CCDC66, CEP290 and PCM1. Ciliogenesis, ciliary recruitment of BBS4 and centriolar satellite organization are impaired in cells depleted for CCDC66. Taken together, our findings identify CCDC66 as a targeting factor for centrosome and cilium proteins.
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    PublicationOpen Access
    Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation
    (Wiley, 2019) Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Odabaşı, Ezgi; Karalar, Elif Nur Fırat; Gül, Şeref; Kavaklı, İbrahim Halil; Other; Researcher; Faculty Member; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; N/A; 206349; N/A; 40319
    Centriolar satellites are ubiquitous in vertebrate cells. They have recently emerged as key regulators of centrosome/cilium biogenesis, and their mutations are linked to ciliopathies. However, their precise functions and mechanisms of action remain poorly understood. Here, we generated a kidney epithelial cell line (IMCD3) lacking satellites by CRISPR/Cas9-mediated PCM1 deletion and investigated the cellular and molecular consequences of satellite loss. Cells lacking satellites still formed full-length cilia but at significantly lower numbers, with changes in the centrosomal and cellular levels of key ciliogenesis factors. Using these cells, we identified new ciliary functions of satellites such as regulation of ciliary content, Hedgehog signaling, and epithelial cell organization in three-dimensional cultures. However, other functions of satellites, namely proliferation, cell cycle progression, and centriole duplication, were unaffected in these cells. Quantitative transcriptomic and proteomic profiling revealed that loss of satellites affects transcription scarcely, but significantly alters the proteome. Importantly, the centrosome proteome mostly remains unaltered in the cells lacking satellites. Together, our findings identify centriolar satellites as regulators of efficient cilium assembly and function and provide insight into disease mechanisms of ciliopathies.