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

Shin JH, Bae DJ, Kim ES, Kim HB, Park SJ, Jo YK, Jo DS, Jo DG, Kim SY, Cho DH - Biomol Ther (Seoul) (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701.

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.

No MeSH data available.


Related in: MedlinePlus

Autophagy mediates mefloquine-induced elongation of primary cilia in htRPE cells. (A) htRPE/Smo-GFP cells pre-treated with 3MA (5 mM) for 12 h were further incubated with Meflo (10 μM) for 24 h. Ciliated cells were counted under a fluorescence microscope. (B) htRPE/Smo-GFP cells transfected with Sc or siATG5 were further treated with Meflo (10 μM) for 24 h. Ciliated cells were counted under a fluorescence microscope. Data were obtained from at least three independent experiments, and values are presented as the means ± S.E.M. (*p<0.05).
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f4-bt-23-327: Autophagy mediates mefloquine-induced elongation of primary cilia in htRPE cells. (A) htRPE/Smo-GFP cells pre-treated with 3MA (5 mM) for 12 h were further incubated with Meflo (10 μM) for 24 h. Ciliated cells were counted under a fluorescence microscope. (B) htRPE/Smo-GFP cells transfected with Sc or siATG5 were further treated with Meflo (10 μM) for 24 h. Ciliated cells were counted under a fluorescence microscope. Data were obtained from at least three independent experiments, and values are presented as the means ± S.E.M. (*p<0.05).

Mentions: Because mefloquine induces both autophagy and elongation of primary cilia in htRPE cells, we further investigated the effect of autophagy on the formation of primary cilia in mefloquine-treated cells. Interestingly, inhibition of autophagy by 3MA significantly suppressed the number of ciliated cells induced by treatment with mefloquine (Fig. 4A). Consistently, down-regulation of ATG5 also markedly blocked the mefloquine-induced formation of primary cilia in htRPE cells (Fig. 4B). These results suggested that autophagy positively regulates the elongation of primary cilia in mefloquine-treated RPE cells.


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

Shin JH, Bae DJ, Kim ES, Kim HB, Park SJ, Jo YK, Jo DS, Jo DG, Kim SY, Cho DH - Biomol Ther (Seoul) (2015)

Autophagy mediates mefloquine-induced elongation of primary cilia in htRPE cells. (A) htRPE/Smo-GFP cells pre-treated with 3MA (5 mM) for 12 h were further incubated with Meflo (10 μM) for 24 h. Ciliated cells were counted under a fluorescence microscope. (B) htRPE/Smo-GFP cells transfected with Sc or siATG5 were further treated with Meflo (10 μM) for 24 h. Ciliated cells were counted under a fluorescence microscope. Data were obtained from at least three independent experiments, and values are presented as the means ± S.E.M. (*p<0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4489826&req=5

f4-bt-23-327: Autophagy mediates mefloquine-induced elongation of primary cilia in htRPE cells. (A) htRPE/Smo-GFP cells pre-treated with 3MA (5 mM) for 12 h were further incubated with Meflo (10 μM) for 24 h. Ciliated cells were counted under a fluorescence microscope. (B) htRPE/Smo-GFP cells transfected with Sc or siATG5 were further treated with Meflo (10 μM) for 24 h. Ciliated cells were counted under a fluorescence microscope. Data were obtained from at least three independent experiments, and values are presented as the means ± S.E.M. (*p<0.05).
Mentions: Because mefloquine induces both autophagy and elongation of primary cilia in htRPE cells, we further investigated the effect of autophagy on the formation of primary cilia in mefloquine-treated cells. Interestingly, inhibition of autophagy by 3MA significantly suppressed the number of ciliated cells induced by treatment with mefloquine (Fig. 4A). Consistently, down-regulation of ATG5 also markedly blocked the mefloquine-induced formation of primary cilia in htRPE cells (Fig. 4B). These results suggested that autophagy positively regulates the elongation of primary cilia in mefloquine-treated RPE cells.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701.

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.

No MeSH data available.


Related in: MedlinePlus