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Merck

Autophagy Regulates Formation of Primary Cilia in Mefloquine-Treated Cells.

Biomolecules & therapeutics (2015-07-15)
Ji Hyun Shin, Dong-Jun Bae, Eun Sung Kim, Han Byeol Kim, So Jung Park, Yoon Kyung Jo, Doo Sin Jo, Dong-Gyu Jo, Sang-Yeob Kim, Dong-Hyung Cho
RESUMEN

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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