The septin complex links the catenin complex to the actin cytoskeleton for establishing epithelial cell polarity  

作　　者：Xueying Wang Wenwen Wang Xiwei Wang Ming Wang Lijuan Zhu Fatima Garba Chuanhai Fu Barbara Zieger Xu Liu Xing Liu Xuebiao Yao 

机构地区：[1]MOE Key Laboratory for Membraneless Organelles&Cellular Dynamics and Hefei National Laboratory for Physical Sciences at the Microscale,University of Science and Technology of China,Hefei 230027,China [2]Keck Center for Organoids Plasticity Control,Atlanta,GA 30310,USA [3]Anhui Key Laboratory for Cellular Dynamics&Chemical Biology and CAS Center for Excellence in Molecular Cell Science,Hefei 230027,China [4]Department of Pediatrics and Adolescent Medicine,Division of Pediatric Hematology and Oncology,Medical Center,Faculty of Medicine,University of Freiburg,79106 Freiburg,Germany

出　　处：《Journal of Molecular Cell Biology》2021年第6期395-408,共14页分子细胞生物学报（英文版）

基　　金：This work was supported in part by grants from the National Natural Science Foundation of China(31621002,32090040,21922706,91854203,91853115,81630080,31430054,and 31671405);National Key Research and Development Program of China(2017YFA0503600,2016YFA0100500,and 2016YFA0101200);the Ministry of Education(IRT_17R102,20113402130010);the Strategic Priority Research Program of Chinese Academy of Sciences(XDB19000000);the Fundamental Research Funds for the Central Universities(WK2340000066 and WK207000019A);National Institutes of Health Grants(CA164133,DK115812,and DK56292).

摘　　要：Cell polarity is essential for spatially regulating of physiological processes in metazoans by which hormonal stimulation‒secretion coupling is precisely coupled for tissue homeostasis and organ communications.However,the molecular mechanisms underlying epithelial cell polarity establishment remain elusive.Here,we show that septin cytoskeleton interacts with catenin complex to organize a functional domain to separate apical from basal membranes in polarized epithelial cells.Using polarized epithelial cell monolayer as a model system with transepithelial electrical resistance as functional readout,our studies show that septins are essential for epithelial cell polarization.Our proteomic analyses discovered a novel septin‒catenin complex during epithelial cell polarization.The functional relevance of septin‒catenin complex was then examined in three-dimensional(3D)culture in which suppression of septins resulted in deformation of apical lumen in cysts,a hallmark seen in polarity-deficient 3D cultures and animals.Mechanistically,septin cytoskeleton stabilizes the association of adherens catenin complex with actin cytoskeleton,and depletion or disruption of septin cytoskeleton liberates adherens junction and polarity complexes into the cytoplasm.Together,these findings reveal a previously unrecognized role for septin cytoskeleton in the polarization of the apical‒basal axis and lumen formation in polarized epithelial cells.

关 键 词：SEPTIN CYTOSKELETON cell polarity adherens junction epithelial cells 

分 类 号：Q25[生物学—细胞生物学]