Centrioles, which function as the essential template for ciliogenesis, are carefully maintained through different levels of regulation in vertebrate cycling cells. For example, we found that centrioles are converted to centrosomes (or the microtubule organization center) through stepwise modifications in a process called centriole-to-centrosome conversion (CCC). CCC enables the modified centriole, or the centrosome, to duplicate in S phase and to segregate equally in mitosis via the spindle, ensuring centriole/centrosome homeostasis. In addition, the presence and quality of the centrosome is further monitored by a separate surveillance program working with p53-mediated stress signaling to remove cells that have no or defective centrosomes. Finally, during vertebrate ciliogenesis, the centrosome can function more than just a template ? centrosomes are positioned deeply inside the cells where they organize microtubules and Golgi-mediated trafficking to regulate the spatial configuration of primary cilia, producing a mysterious type of cilia called submerged cilia. Instead of being at the cell surface as seen for typical cilia, submerged cilia are deliberately hidden by cells in a deep membrane invagination for reasons completely unknown. In this proposal, we seek to understand the molecular control of CCC, centrosome surveillance, and submerged cilia biogenesis.
s Centrosome and cilia dysfunction is prevalent in a wide range of diseases collectively called ciliopathy, including e.g. Bardet-Biedl syndrome, Joubert syndrome, Meckel-Gruber syndrome, polycystic kidney disease, and primary ciliary dyskinesia. However, the physiological role that these organelles play in most tissues remains elusive. A thorough understanding of the molecular pathways vertebrate cells employ to form and maintain the centrosome-cilium complex will allow for the development of therapeutic manipulations for some of these diseases.
|Fong, Chii Shyang; Ozaki, Kanako; Tsou, Meng-Fu Bryan (2018) PPP1R35 ensures centriole homeostasis by promoting centriole-to-centrosome conversion. Mol Biol Cell 29:2801-2808|
|Yang, T Tony; Chong, Weng Man; Wang, Won-Jing et al. (2018) Super-resolution architecture of mammalian centriole distal appendages reveals distinct blade and matrix functional components. Nat Commun 9:2023|
|Shulman, Avital S; Tsou, Meng-Fu Bryan (2017) Probing Cilia-Associated Signaling Proteomes in Animal Evolution. Dev Cell 43:653-655|
|Fong, Chii Shyang; Mazo, Gregory; Das, Tuhin et al. (2016) 53BP1 and USP28 mediate p53-dependent cell cycle arrest in response to centrosome loss and prolonged mitosis. Elife 5:|
|Mazo, Gregory; Soplop, Nadine; Wang, Won-Jing et al. (2016) Spatial Control of Primary Ciliogenesis by Subdistal Appendages Alters Sensation-Associated Properties of Cilia. Dev Cell 39:424-437|
|Kim, Minhee; O'Rourke, Brian P; Soni, Rajesh Kumar et al. (2016) Promotion and Suppression of Centriole Duplication Are Catalytically Coupled through PLK4 to Ensure Centriole Homeostasis. Cell Rep 16:1195-1203|
|Soni, Rajesh Kumar; Tsou, Meng-Fu Bryan (2016) A Cell-Free System for Real-Time Analyses of Centriole Disengagement and Centriole-to-Centrosome Conversion. Methods Mol Biol 1413:197-206|
|Wang, Won-Jing; Acehan, Devrim; Kao, Chien-Han et al. (2015) De novo centriole formation in human cells is error-prone and does not require SAS-6 self-assembly. Elife 4:|
|Yang, T Tony; Su, Jimmy; Wang, Won-Jing et al. (2015) Superresolution Pattern Recognition Reveals the Architectural Map of the Ciliary Transition Zone. Sci Rep 5:14096|
|Kim, Minhee; Fong, Chii Shyang; Tsou, Meng-Fu Bryan (2014) Centriole duplication: when PLK4 meets Ana2/STIL. Curr Biol 24:R1046-8|
Showing the most recent 10 out of 18 publications