Actin nucleator formins regulate the tension-buffering function of caveolin-1.
Actin nucleator formins regulate the tension-buffering function of caveolin-1.
复制标题
肌动蛋白成核剂formins调节小窝蛋白-1的张力缓冲功能。
DOI：
10.1093/jmcb/mjab070
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发表时间：
2022-01-29
影响因子：
5.5
通讯作者：
Jiu Y
中科院分区：
文献类型：
--
作者：
Shi X;Tang D;Xing Y;Zhao S;Fan C;Zhong J;Cui Y;Shi K;Jiu Y
机械敏感的肌动蛋白细胞骨架和小窝均参与细胞迁移、形态发生和囊泡运输等主动过程。尽管对不同的肌动蛋白成分已有深入研究，但它们如何作用于细胞质小窝，尤其是在机械应力环境下，仍不明确。在此，我们确定了由小窝蛋白 - 1（CAV - 1）标记的细胞内囊泡的两种与肌动蛋白相关的运动模式，即 “驻留” 和 “往返驻留”。为探究其不同动态的原因，我们对伸长的与肌动蛋白相关的成蛋白功能进行了干扰。通过化学处理和成蛋白基因的RNA沉默，我们发现缺乏肌动蛋白成核因子成蛋白会导致细胞质CAV - 1囊泡密度急剧降低、聚集增加且运动性受损。此外，在阻断成蛋白后，低渗刺激引起的CAV - 1减少显著加剧。在成蛋白抑制条件下，细胞在软质底物上培养时CAV - 1囊泡的聚集也会加重。综上所述，我们揭示了与肌动蛋白相关的成蛋白对于维持细胞质CAV - 1的动态组织及其在机械刺激下的敏感性至关重要。我们得出结论，张力调控的肌动蛋白成蛋白就像一个安全阀，减轻CAV - 1上的过度张力，保护CAV - 1免受机械损伤。
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.
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影响因子：
7.8
作者：
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通讯作者：
Bershadsky, Alexander D
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