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Identification of Regulators for Ciliary Disassembly by a Chemical Screen

Authors :
Junmin Pan
Zhijun Dong
Jia Xu
Source :
ACS Chemical Biology. 16:2665-2672
Publication Year :
2021
Publisher :
American Chemical Society (ACS), 2021.

Abstract

Cilia are organelles for cellular signaling and motility. They are assembled in G0/G1 and disassembled prior to mitosis. Compared to what is known about ciliary assembly, less is understood about ciliary disassembly. To uncover new mechanisms of ciliary disassembly, we performed an unbiased chemical screen. Chlamydomonas reinhardtii cells were experimentally induced for ciliary disassembly by treatment with sodium pyrophosphate. An FDA approved drug library (HY-L022P-1, MedChemExpress) was used for the screening. Primary screening with further experiments has identified microtubule stabilizer taxanes, CDK4/6 inhibitor abemaciclib and Raf inhibitor dabrafenib being effective in inhibiting ciliary disassembly induced experimentally but also under physiological conditions. In addition, their effects on ciliary disassembly in mammalian cells has also been confirmed. Thus, our studies have not only revealed new mechanisms in ciliary disassembly but also provided new tools for studying ciliary disassembly. These discovered drugs may be used for therapeutic interventions of disorders involving ciliary degeneration such as retinopathies.

Details

ISSN :
15548937 and 15548929
Volume :
16
Database :
OpenAIRE
Journal :
ACS Chemical Biology
Accession number :
edsair.doi.dedup.....1eb1e87d7a5fb7c052bd01434f624d99