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Indexed at: search.filters.indexed.PubMedSubject: search.filters.subject.Centrioles

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    Prolonged overexpression of PLK4 leads to formation of centriole rosette clusters that are connected via canonical centrosome linker proteins
    (Nature Portfolio, 2024) Özcan, Selahattin Can; Kalkan, Batuhan Mert; Çiçek, Enes; Canbaz, Ata Alpay; Ayhan, Ceyda Açılan; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine
    Centrosome amplification is a hallmark of cancer and PLK4 is one of the responsible factors for cancer associated centrosome amplification. Increased PLK4 levels was also shown to contribute to generation of cells with centriole amplification in mammalian tissues as olfactory neuron progenitor cells. PLK4 overexpression generates centriole rosette (CR) structures which harbor more than two centrioles each. Long term PLK4 overexpression results with centrosome amplification, but the maturation of amplified centrioles in CRs and linking of PLK4 induced amplified centrosomes has not yet been investigated in detail. Here, we show evidence for generation of large clustered centrosomes which have more than 2 centriole rosettes and define these structures as centriole rosette clusters (CRCs) in cells that have high PLK4 levels for 2 consecutive cell cycles. In addition, we show that PLK4 induced CRs follow normal centrosomal maturation processes and generate CRC structures that are inter-connected with canonical centrosomal linker proteins as C-Nap1, Rootletin and Cep68 in the second cell cycle after PLK4 induction. Increased PLK4 levels in cells with C-Nap1 and Rootletin knock-out resulted with distanced CRs and CRCs in interphase, while Nek2 knock-out inhibited separation of CRCs in prometaphase, providing functional evidence for the binding of CRC structures with centrosomal linker proteins. Taken together, these results suggest a cell cycle dependent model for PLK4 induced centrosome amplification which occurs in 2 consecutive cell cycles: (i) CR state in the first cell cycle, and (ii) CRC state in the second cell cycle.
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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.