首页|Pathologically relevant aldoses and environmental aldehydes cause cilium disassembly via formyl group-mediated mechanisms
Pathologically relevant aldoses and environmental aldehydes cause cilium disassembly via formyl group-mediated mechanisms
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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.
Haihe Laboratory of Cell Ecosystem,State Key Laboratory of Medicinal Chemical Biology,Tianjin Key Laboratory of Protein Science,College of Life Sciences,Nankai University,Tianjin 300071,China
Laboratory of Tissue Homeostasis,Haihe Laboratory of Cell Ecosystem,Tianjin 300462,China
Center for Cell Structure and Function,Collaborative Innovation Center of Cell Biology in Universities of Shandong,Shandong Provincial Key Laboratory of Animal Resistance Biology,College of Life Sciences,Shandong Normal University,Jinan 250014,China
National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Key R&D Program of China
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