PDF(Pubmed)
Abstract：
Membrane expansion integrates multiple forces to mediate precise tube growth and network formation. Defects lead to deformations, as found in diseases such as polycystic kidney diseases, aortic aneurysms, stenosis, and tortuosity. We identified a mechanism of sensing and responding to the membrane-driven expansion of tracheal tubes. The apical membrane is anchored to the apical extracellular matrix (aECM) and causes expansion forces that elongate the tracheal tubes. The aECM provides a mechanical tension that balances the resulting expansion forces, with Dumpy being an elastic molecule that modulates the mechanical stress on the matrix during tracheal tube expansion. We show in Drosophila that the zona pellucida (ZP) domain protein Piopio interacts and cooperates with the ZP protein Dumpy at tracheal cells. To resist shear stresses which arise during tube expansion, Piopio undergoes ectodomain shedding by the Matriptase homolog Notopleural, which releases Piopio-Dumpy-mediated linkages between membranes and extracellular matrix. Failure of this process leads to deformations of the apical membrane, tears the apical matrix, and impairs tubular network function. We also show conserved ectodomain shedding of the human TGFβ type III receptor by Notopleural and the human Matriptase, providing novel findings for in-depth analysis of diseases caused by cell and tube shape changes.
摘要：
膜膨胀整合了多种力以调节精确的管生长和网络形成。缺陷导致变形，如在多囊肾疾病等疾病中发现的，主动脉瘤,狭窄,和弯曲。我们确定了一种感知和响应气管导管膜驱动扩张的机制。顶端膜锚定到顶端细胞外基质(aECM),并引起伸长气管导管的膨胀力。aECM提供机械张力，平衡所产生的膨胀力，Dumpy是一种弹性分子，可在气管导管扩张过程中调节基质上的机械应力。我们在果蝇中显示透明带（ZP）结构域蛋白Piopio与气管细胞上的ZP蛋白Dumpy相互作用并合作。为了抵抗在管膨胀过程中产生的剪切应力，Piopio通过Matriptase同源物Notocribal经历了胞外域脱落，在膜和细胞外基质之间释放Piopio-Dumpy介导的连接。此过程的失败导致根尖膜的变形，撕裂顶端基质，并损害管状网络功能。我们还显示了人TGFβIII型受体的保守的胞外域脱落，为深入分析由细胞和管形状变化引起的疾病提供了新的发现。
