BACKGROUND The Piezo gene encodes a highly conserved cell membrane protein responsible for sensing pressure. The glomerular kidney and the slit diaphragm filtration structure depend on pressure for filtration. However, how Piezo is involved in kidney function and in maintaining the slit diaphragm filtration structure is not clear. METHODS We used Drosophila pericardial nephrocytes, filtration kidney cells with striking structural and functional similarities to human podocytes, in a loss-of-function model (mutant and knockdown) to study the roles of Piezo in nephrocyte filtration and function. RESULTS Piezo is highly expressed at the invaginated membranes (lacuna channels) of nephrocytes. A Piezo loss-of-function mutant showed significant nephrocyte functional decline. Nephrocyte-specific silencing of Piezo showed disruption of the slit diaphragm filtration structure and significant functional defects. Electron microscopy showed that silencing Piezo in nephrocytes leads to reduced slit diaphragm density and abnormal shape of lacuna channels. Moreover, the Piezo-deficient nephrocytes showed internalized slit diaphragm component proteins, reduced autophagy, increased ER stress, and reduced calcium influx. CONCLUSIONS Together, our findings suggest that Piezo plays an important role in the calcium homeostasis of nephrocytes and is required for maintaining nephrocyte function and the slit diaphragm filtration structure.

中文翻译：

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果蝇的压电、肾细胞功能和裂隙隔膜维持。


背景 Piezo 基因编码一种高度保守的细胞膜蛋白，负责感应压力。肾小球肾和狭缝隔膜过滤结构取决于过滤压力。然而，压电陶瓷如何参与肾功能和维持狭缝隔膜过滤结构尚不清楚。方法 我们使用果蝇心包肾细胞，在功能丧失模型 （突变和敲除） 中过滤与人类足细胞具有显着结构和功能相似的肾细胞，以研究压电陶瓷在肾细胞滤过和功能中的作用。结果 压电在肾细胞的内陷膜（腔隙通道）高度表达。压电功能丧失突变体显示肾细胞功能显着下降。压电陶瓷的肾细胞特异性沉默显示狭缝隔膜过滤结构的破坏和明显的功能缺陷。电子显微镜显示，沉默肾细胞中的压电陶瓷会导致裂隙隔膜密度降低和腔隙通道形状异常。此外，压电缺陷型肾细胞显示内化的狭缝隔膜成分蛋白，自噬减少，ER 应激增加，钙内流减少。结论 综上所述，我们的研究结果表明，压电陶瓷在肾细胞的钙稳态中起重要作用，是维持肾细胞功能和狭缝隔膜过滤结构所必需的。