Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Autophagy Regulates Formation of Primary Cilia in Mefloquine-Treated Cells

  • Shin, Ji Hyun (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Bae, Dong-Jun (ASAN Institute for Life Science, University of Ulsan College of Medicine, ASAN Medical Center) ;
  • Kim, Eun Sung (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Kim, Han Byeol (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Park, So Jung (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Jo, Yoon Kyung (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Jo, Doo Sin (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Jo, Dong-Gyu (The School of Pharmacy, Sungkyunkwan University) ;
  • Kim, Sang-Yeob (ASAN Institute for Life Science, University of Ulsan College of Medicine, ASAN Medical Center) ;
  • Cho, Dong-Hyung (Graduate School of East-West Medical Science, Kyung Hee University)
  • Received : 2015.03.05
  • Accepted : 2015.04.20
  • Published : 2015.07.01
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Abstract

Primary cilia have critical roles in coordinating multiple cellular signaling pathways. Dysregulation of primary cilia is implicated in various ciliopathies. To identify specific regulators of autophagy, we screened chemical libraries and identified mefloquine, an anti-malaria medicine, as a potent regulator of primary cilia in human retinal pigmented epithelial (RPE) cells. Not only ciliated cells but also primary cilium length was increased in mefloquine-treated RPE cells. Treatment with mefloquine strongly induced the elongation of primary cilia by blocking disassembly of primary cilium. In addition, we found that autophagy was increased in mefloquine-treated cells by enhancing autophagic flux. Both chemical and genetic inhibition of autophagy suppressed ciliogenesis in mefloquine-treated RPE cells. Taken together, these results suggest that autophagy induced by mefloquine positively regulates the elongation of primary cilia in RPE cells.

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References

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