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 cont...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.展开更多
Introduction Cell mechanosensing is the process that cell senses extracellular mechanical cues through mechanosensors and transduces them to downstream signaling pathways to alter cell mechanics and behaviors,which is...Introduction Cell mechanosensing is the process that cell senses extracellular mechanical cues through mechanosensors and transduces them to downstream signaling pathways to alter cell mechanics and behaviors,which is involved in embryonic development(Gaetani et al.,2020),tissue regeneration(Fu et al.,2019),inflammatory response(Worbs et al.,2017),and tumor invasion and metastasis(Gargalionis et al.,2018).This ability is crucial for cells to adapt to mechanical stimuli(compressive force,shear stress,substrate rigidity,topology,adhesiveness,etc.)and maintain homeostasis(Chen et al.,2017).展开更多
基金the Key Research and Development Program,Ministry of Science and Technology of China(2022YFC2303502 and 2021YFC2300204)the Chinese Academy of Sciences-Vice Presidency Science and Technology Silk Road Science Fund(GJHZ2021138)+2 种基金the National Natural Science Foundation of China(32222022,92054104,31970660,31925025,and 22293033)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29050201)the R&D Program of Guangzhou Laboratory(SRPG22-002)。
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)+2 种基金Shanghai Municipal Science and Technology Major Project(2019SHZDZX02)Natural Science Foundation of Shanghai(19ZR1463000)‘100 Talents Program’from the Chinese Academy of Sciences.
文摘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.
基金supported by the National Key Research and Development Program of China(2022YFC2303502 and 2021YFC2300204)the National Natural Science Foundation of China(32222022,92054104,and 31970660)+1 种基金CAS-VPST Silk Road Science Fund(GJHZ2021138)Shanghai Municipal Science and Technology Major Project(2019SHZDZX02).
文摘Introduction Cell mechanosensing is the process that cell senses extracellular mechanical cues through mechanosensors and transduces them to downstream signaling pathways to alter cell mechanics and behaviors,which is involved in embryonic development(Gaetani et al.,2020),tissue regeneration(Fu et al.,2019),inflammatory response(Worbs et al.,2017),and tumor invasion and metastasis(Gargalionis et al.,2018).This ability is crucial for cells to adapt to mechanical stimuli(compressive force,shear stress,substrate rigidity,topology,adhesiveness,etc.)and maintain homeostasis(Chen et al.,2017).
