Tension-dependent RHGF-1 recruitment to stress fibers drives robust spermathecal tissue contraction.
Tension-dependent RHGF-1 recruitment to stress fibers drives robust spermathecal tissue contraction.
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DOI：
10.1083/jcb.202203105
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发表时间：
2023-02-06
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影响因子：
--
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中科院分区：
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Avivi Kela等人。在线虫受精囊中发现了一条新的机械转导途径，涉及Rhogef依赖张力的定位和Rho-1-MyosinII激活的正反馈环，使上皮管能够感知管腔压力并调节其收缩能力作为响应。收缩上皮管存在于各种器官中，如肺气道和毛细血管。它们感知管腔压力并以足够的收缩能力做出反应的能力对它们的生理至关重要，它的错误调节会导致哮喘和高血压等疾病。在这里，我们描述了组织拉伸下游的机械响应调节途径，它控制线虫受精膜的收缩，这是一种发生受精的管状结构。使用实时成像，我们发现排卵诱导的精囊细胞拉伸导致Rhogef RHGF-1招募到应激纤维，从而在正反馈环路中激活Rho-1和肌球蛋白II。通过缺失分析，我们确定了RHGF-1的PDZ结构域负责与F-肌动蛋白结合，并且与RhoGAP SPV-1的遗传上位性分析表明，张力依赖的RHGF-1对F-肌动蛋白的募集是强大的精膜收缩所必需的。我们的研究阐明了Rho GTP酶的机械敏感性调节器如何为上皮细胞提供调节其收缩能力以响应内部压力的能力。
Avivi Kela et al. discovered a novel mechanotransduction pathway in the C. elegans spermatheca involving tension-dependent localization of a RhoGEF and a positive feedback loop for RHO-1–MyosinII activation that gives an epithelial tube the ability to sense luminal pressure and adjust its contractility in response. Contractile epithelial tubes are found in various organs, such as lung airways and blood capillaries. Their ability to sense luminal pressure and respond with adequate contractility is essential for their physiology, and its mis-regulation results in diseases such as asthma and hypertension. Here, we describe a mechanoresponsive regulatory pathway downstream of tissue stretching that controls contraction of the C. elegans spermatheca, a tubular structure where fertilization occurs. Using live-imaging, we show that ovulation-induced stretching of spermathecal cells leads to recruitment of the RhoGEF RHGF-1 to stress fibers, which activates RHO-1 and myosin II in a positive feedback loop. Through deletion analysis, we identified the PDZ domain of RHGF-1 as responsible for F-actin binding, and genetic epistasis analysis with the RhoGAP spv-1 demonstrated that tension-dependent recruitment of RHGF-1 to F-actin is required for robust spermathecal contractility. Our study illustrates how mechanosensitive regulators of Rho GTPases provide epithelial tubes the ability to tune their contractility in response to internal pressure.
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DOI：
10.1016/j.cub.2011.12.010
发表时间：
2012-02-07
期刊：
Current biology : CB
影响因子：
--
作者：
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通讯作者：
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影响因子：
3.3
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影响因子：
16.6
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