Pathologically relevant aldoses and environmental aldehydes cause cilium disassembly via formyl group-mediated mechanisms

病理相关的醛糖和环境醛通过甲酰基介导的机制引起纤毛分解

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作者:Te Li, Min Liu, Fan Yu, Song Yang, Weiwen Bu, Kai Liu, Jia Yang, Hua Ni, Mulin Yang, Hanxiao Yin, Renjie Hong, Dengwen Li, Huijie Zhao, Jun Zhou

Abstract

Carbohydrate metabolism disorders (CMDs), such as diabetes, galactosemia, and mannosidosis, cause ciliopathy-like multiorgan defects. However, the mechanistic link of cilia to CMD complications is still poorly understood. Herein, we describe significant cilium disassembly upon treatment of cells with pathologically relevant aldoses rather than the corresponding sugar alcohols. Moreover, environmental aldehydes are able to trigger cilium disassembly by the steric hindrance effect of their formyl groups. Mechanistic studies reveal that aldehydes stimulate extracellular calcium influx across the plasma membrane, which subsequently activates the calmodulin-Aurora A-histone deacetylase 6 pathway to deacetylate axonemal microtubules and triggers cilium disassembly. In vivo experiments further show that Hdac6 knockout mice are resistant to aldehyde-induced disassembly of tracheal cilia and sperm flagella. These findings reveal a previously unrecognized role for formyl group-mediated cilium disassembly in the complications of CMDs.

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