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

• 作者: Xuemeng Shi Daijiao Tang Yifan Xing Shuangshuang Zhao Changyuan Fan Jin Zhong Yanqin Cui Kun Shi Yaming Jiu
• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2021,（12）
• 所属期刊栏目: Articles
• 页码范围: 876-888
• 页数: 13页
• 语种: 英文
• DOI: 10.1093/jmcb/mjab070

摘要

Both the mechanosensitive actin cytoskeleton and caveolae contribute to active processes such as cell migration,morphogene-sis,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.