Identification of Regulators for Ciliary Disassembly by a Chemical Screen

ACS Chem Biol. 2021 Nov 19;16(11):2665-2672. doi: 10.1021/acschembio.1c00823. Epub 2021 Nov 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines / pharmacology*
  • Benzimidazoles / pharmacology*
  • Biological Transport
  • Cell Cycle / drug effects
  • Cell Line, Transformed
  • Chlamydomonas reinhardtii / drug effects*
  • Cilia / drug effects*
  • Diphosphates / pharmacology*
  • Humans
  • Imidazoles / pharmacology*
  • Oximes / pharmacology*
  • Taxoids / pharmacology*

Substances

  • Aminopyridines
  • Benzimidazoles
  • Diphosphates
  • Imidazoles
  • Oximes
  • Taxoids
  • abemaciclib
  • sodium pyrophosphate
  • dabrafenib