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

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 

机构地区：[1]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 [2]Laboratory of Tissue Homeostasis,Haihe Laboratory of Cell Ecosystem,Tianjin 300462,China [3]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

出　　处：《Journal of Molecular Cell Biology》2024年第1期15-28,共14页分子细胞生物学报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(31991193 and 32230025);the National Key R&D Program of China(2021YFA1101001).

摘　　要：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.

关 键 词：carbohydrate metabolism disorder ALDOSE ALDEHYDE cilium disassembly formyl group calcium influx HDAC6 

分 类 号：O62[理学—有机化学]