“Centriolar satellites are required for the biogenesis and function of the centrosome/cilium complex”
Assoc. Prof. Elif N. Firat-Karalar
Department of Molecular Biology and Genetics, Koç University
Dr. Elif Nur Firat-Karalar studied molecular biology and genetics at Bilkent University, Turkey. She then moved to US for her PhD work at the University of California, Berkeley, where she investigated the mechanisms of actin nucleation under the supervision of Matthew Welch. During her postdoctoral work in the laboratory of Tim Stearns at Stanford University, she used proteomics approaches and identified the centriole proteome and proximity interactome that revealed novel regulatory pathways for centriole biogenesis. In 2014, Elif became an Assistant Professor at Koç University in Istanbul (Turkey). Research in her lab focuses on studying the structure and function of the mammalian centrosome/cilium complex, with a particular focus on centriolar satellites. Elif is the recipient of an ERC Starting Grant, EMBO installation grant, Royal Society Newton Advanced Fellowship and EMBO Young Investigator Award. She has been awarded with L’Oreal-UNESCO Women In Science Award, Sabri Ulker Science Award and TUBITAK Health Sciences Incentive Award. Dr. Fırat Karalar’s project grant proposal has been accepted for funding by the Istanbul Development Agency (ISTKA) regarding 2021 Innovative Istanbul Financial Support Program.
The centrosome/cilium complex is required for key functions ranging from cell division to cellular signaling and its deregulation causes various human diseases including cancer and ciliopathies. To elucidate disease mechanisms, it is essential to determine how centrosomes and cilia assemble and function in time and in space. To this end, we have focused on studying the vertebrate-specific components of the centrosome cilium complex, centriolar satellites, which are an array of membrane-less granules that localize around the centrosome/cilium complex. Although mutations affecting centriolar satellites were linked to ciliopathies, their precise functions, mechanisms and the functional significance of their typical clustering around the centrosomes remain poorly understood. To determine their cellular functions as discrete protein complexes, we generated satellite-less retinal pigmental and kidney epithelial cells and investigated the cellular and molecular consequence of satellite-loss. While satellites were essential for cilium assembly in retinal epithelial cells, satellite-less kidney epithelial cells still formed full-length cilia but at significantly lower levels, with changes in the centrosomal and cellular levels of key ciliogenesis factors. Furthermore, we identified the first satellite-specific functions at cilia, specifically in regulating ciliary content, Hedgehog signalling, and epithelial cell organization. Next, we investigated the functional significance of why satellites cluster around the centrosomes in most cell types. To this end, we employed a chemically inducible trafficking approach to restrict satellite localization at the cell periphery or the centrosome. Using these cells, we determined which proteins redistribute along with satellites and thereby are regulated by them. By studying the phenotypic consequences of satellite redistribution, we identified functions for centriolar satellites in cilium assembly and maintenance. Together, our findings reveal that satellites regulate show that the satellites are required for efficient centrosome and cilium assembly and function and provide insight into disease mechanisms of ciliopathies.
Date-Time: Wednesday, December 8, 2021 at 15:30
Host: Doç. Dr. Işık Yuluğ
***This is an online event. To obtain Zoom link and password, please contact to the department.
All interested are cordially invited.