Researcher:
Deretic, Jovana

Profile Picture
ORCID

Job Title

Researcher

First Name

Jovana

Last Name

Deretic

Name

Name Variants

Deretic, Jovana

Email Address

Birth Date

Filters

2022 - 20233

Advanced Search

Filter by

Settings

Researcher Of Publications: search.filters.isAuthorOfPublication.4ddbd03b-8cf4-4659-9c89-e3194d0ccfe2

Search Results

Now showing 1 - 3 of 3
  • Placeholder
    PublicationMetadata only
    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.
  • Thumbnail Image
    PublicationOpen Access
    ENKD1 is a centrosomal and ciliary microtubule-associated protein important for primary cilium content regulation
    (Wiley, 2022) Department of Molecular Biology and Genetics; Department of Molecular Biology and Genetics; Tiryaki, Fatmanur; Deretic, Jovana; Karalar, Elif Nur Fırat; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; 206349
    Centrioles and cilia are conserved, microtubule-based structures critical for cell function and development. Their dysfunction causes cancer and developmental disorders. How microtubules are organized into ordered structures by microtubule-associated proteins (MAPs) and tubulin modifications is best understood during mitosis but is largely unexplored for the centrioles and the ciliary axoneme, which are composed of stable microtubules that maintain their length at a steady-state. In particular, we know little about the identity of the centriolar and ciliary MAPs and how they work together during the assembly and maintenance of the cilium and centriole. Here, we identified the Enkurin domain containing 1 (ENKD1) as a component of the centriole wall and the axoneme in mammalian cells and showed that it has extensive proximity interactions with these compartments and MAPs. Using in vitro and cellular assays, we found that ENKD1 is a new MAP that regulates microtubule organization and stability. Consistently, we observed an increase in tubulin polymerization and microtubule stability, as well as disrupted microtubule organization in ENKD1 overexpression. Cells depleted for ENKD1 were defective in ciliary length and content regulation and failed to respond to Hedgehog pathway activation. Together, our results advance our understanding of the functional and regulatory relationship between MAPs and the primary cilium.
  • Thumbnail Image
    PublicationOpen Access
    The ciliopathy protein CCDC66 controls mitotic progression and cytokinesis by promoting microtubule nucleation and organization
    (Public Library of Science, 2022) Department of Molecular Biology and Genetics; Karalar, Elif Nur Fırat; Batman, Umut; Deretic, Jovana; Faculty Member; Department of Molecular Biology and Genetics; School of Medicine; College of Sciences; Graduate School of Sciences and Engineering; Koç University Hospital; 206349; N/A; N/A
    Pselesapseactoiontfeirmmpthoartaallclhoenatdroinlgolfevmeilcsaroreturbepurleesnenutceldecaotriorencatlny:d organization is critical for faithful segregation of cytoplasmic and genetic material during cell division and signaling via the primary cilium in quiescent cells. Microtubule-associated proteins (MAPs) govern assembly, maintenance, and remodeling of diverse microtubule arrays. While a set of conserved MAPs are only active during cell division, an emerging group of MAPs acts as dual regulators in dividing and nondividing cells. Here, we elucidated the nonciliary functions and molecular mechanism of action of the ciliopathy-linked protein CCDC66, which we previously characterized as a regulator of ciliogenesis in quiescent cells. We showed that CCDC66 dynamically localizes to the centrosomes, the bipolar spindle, the spindle midzone, the central spindle, and the midbody in dividing cells and interacts with the core machinery of centrosome maturation and MAPs involved in cell division. Loss-of-function experiments revealed its functions during mitotic progression and cytokinesis. Specifically, CCDC66 depletion resulted in defective spindle assembly and orientation, kinetochore fiber stability, chromosome alignment in metaphase as well as central spindle and midbody assembly and organization in anaphase and cytokinesis. Notably, CCDC66 regulates mitotic microtubule nucleation via noncentrosomal and centrosomal pathways via recruitment of gamma-tubulin to the centrosomes and the spindle. Additionally, CCDC66 bundles microtubules in vitro and in cells by its C-terminal microtubule-binding domain. Phenotypic rescue experiments showed that the microtubule and centrosome-associated pools of CCDC66 individually or cooperatively mediate its mitotic and cytokinetic functions. Collectively, our findings identify CCDC66 as a multifaceted regulator of the nucleation and organization of the diverse mitotic and cytokinetic microtubule arrays and provide new insight into nonciliary defects that underlie ciliopathies.