Research Project: Ccdc66'nın Retina Dejenerasyonundaki Görevinin Ve Çalışma Mekanizmasının Belirlenmesi
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Contributors
Funders
ID
TB.00231
Authors
Karalar, Elif Nur Fırat
Faculty Member
Publications
The centriolar satellite protein CCDC66 interacts with CEP290 and functions in cilium formation and trafficking
(The Company of Biologists (United Kingdom), 2017) Çonkar, Deniz; Culfa, Efraim; Karalar, Elif Nur Fırat; Odabaşı, Ezgi; Rauniyar, Navin; Yates, John R., III; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; Yes; College of Sciences; GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
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.
A proximity mapping journey into the biology of the mammalian centrosome/cilium complex
(Multidisciplinary Digital Publishing Institute (MDPI), 2020) Arslanhan, Melis Dilara; Gülensoy, Dila; Karalar, Elif Nur Fırat; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; Yes; College of Sciences; GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
The mammalian centrosome/cilium complex is composed of the centrosome, the primary cilium and the centriolar satellites, which together regulate cell polarity, signaling, proliferation and motility in cells and thereby development and homeostasis in organisms. Accordingly, deregulation of its structure and functions is implicated in various human diseases including cancer, developmental disorders and neurodegenerative diseases. To better understand these disease connections, the molecular underpinnings of the assembly, maintenance and dynamic adaptations of the centrosome/cilium complex need to be uncovered with exquisite detail. Application of proximity-based labeling methods to the centrosome/cilium complex generated spatial and temporal interaction maps for its components and provided key insights into these questions. In this review, we first describe the structure and cell cycle-linked regulation of the centrosome/cilium complex. Next, we explain the inherent biochemical and temporal limitations in probing the structure and function of the centrosome/cilium complex and describe how proximity-based labeling approaches have addressed them. Finally, we explore current insights into the knowledge we gained from the proximity mapping studies as it pertains to centrosome and cilium biogenesis and systematic characterization of the centrosome, cilium and centriolar satellite interactomes.
