Actin nucleator formins regulate the tension-buffering function of caveolin-1

查看全文 作　　者：Xuemeng [1,2]Shi;Daijiao [3,4]Tang;Yifan [4,5]Xing;Shuangshuang [1,2]Zhao;Changyuan [3,4]Fan;Jin [4,5]Zhong;Yanqin [1,2]Cui;Kun [1,2]Shi;Yaming [1,2,3,4]Jiu 机构地区：[1]The Joint Program in Infection and Immunity,Guangzhou Women and Children’s Medical Center,Guangzhou Medical University,Guangzhou 510623,China;[2]The Joint Program in Infection and Immunity,Institut Pasteur of Shanghai,Chinese Academy of Sciences,Shanghai 200031,China;[3]Unit of Cell Biology and Imaging Study of Pathogen Host Interaction,The Center for Microbes,Development and Health,CAS Key Laboratory of Molecular Virology and Immunology,Institut Pasteur of Shanghai,Chinese Academy of Sciences,Shanghai 200031,China;[4]College of Life Sciences,University of Chinese Academy of Sciences,Beijing 100049,China;[5]Unit of Viral Hepatitis,CAS Key Laboratory of Molecular Virology,Institut Pasteur of Shanghai,Chinese Academy of Sciences,Shanghai 200031,China 出　　处：《Journal of Molecular Cell Biology》索引2021年第13卷第12期,共13页 基　　金：This study was supported by grants from the National Natural Science Foundation of China(92054104 and 31970660);CAS–VPST Silk Road Science Fund 2021(GJHZ2021138);Shanghai Municipal Science and Technology Major Project(2019SHZDZX02);Natural Science Foundation of Shanghai(19ZR1463000);‘100 Talents Program’from the Chinese Academy of Sciences. 摘　　要：Both the mechanosensitive actin cytoskeleton and caveolae contribute to active processes such as cell migration,morphogenesis,and vesicular trafficking.Although distinct actin components are well studied,how they contribute to cytoplasmic caveolae,especially in the context of mechano-stress,has remained elusive.Here,we identify two actin-associated mobility stereotypes of caveolin-1(CAV-1)-marked intracellular vesicles,which are characterized as‘dwelling’and‘go and dwelling’.In order to exploit the reason for their distinct dynamics,elongated actin-associated formin functions are perturbed.We find drastically decreased density,increased clustering,and compromised motility of cytoplasmic CAV-1 vesicles resulting from lacking actin nucleator formins by both chemical treatment and RNA silencing of formin genes.Furthermore,hypo-osmosis-stimulated diminishing of CAV-1 is dramatically intensified upon blocking formins.The clustering of CAV-1 vesicles when cells are cultured on soft substrate is also aggravated under formin inhibition condition.Together,we reveal that actin-associated formins are essential for maintaining the dynamic organization of cytoplasmic CAV-1 and importantly its sensitivity upon mechanical challenge.We conclude that tension-controlled actin formins act as a safety valve dampening excessive tension on CAV-1 and safeguarding CAV-1 against mechanical damage. 关 键 词：CAVEOLIN-1 elongated actin filaments formins hypo-osmotic shock matrix stiffness