An in vitro assay reveals a role for the diaphragm protein PV-1 in endothelial fenestra morphogenesis
An in vitro assay reveals a role for the diaphragm protein PV-1 in endothelial fenestra morphogenesis
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DOI：
10.1073/pnas.0603501103
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发表时间：
2006-11-07
影响因子：
11.1
通讯作者：
Shima, David T.
中科院分区：
文献类型：
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作者：
Ioannidou, Sofia;Deinhardt, Katrin;Shima, David T.
窗孔是肾小球、胃肠道和内分泌腺毛细血管内皮中的小孔，参与血液和组织之间的双向分子交换。虽然几十年的研究已经在超微结构水平上表征了窗孔，但对窗孔形成的机制知之甚少。我们提出了一种体外试验的发展，其中快速和丰富的窗诱导，使他们的生物起源的详细研究。通过使用稳定或分解肌动蛋白微丝的试剂，我们表明肌动蛋白微丝重塑是该模型中窗孔生物发生的一部分。此外，通过使用功能丧失的方法，我们表明，隔膜蛋白PV-1是必要的窗孔结构和有序排列的筛板中的窗孔。总之，这些数据提供了深入了解窗孔形成的细胞生物学，并开辟了未来的窗孔的形态学和生物化学分析相结合的研究。
Fenestrae are small pores in the endothelium of renal glomerular, gastrointestinal, and endocrine gland capillaries and are involved in the bidirectional exchange of molecules between blood and tissues. Although decades of studies have characterized fenestrae at the ultrastructural level, little is known on the mechanisms by which fenestrae form. We present the development of an in vitro assay in which rapid and abundant fenestra induction enables a detailed study of their biogenesis. Through the use of agents that stabilize or disassemble actin microfilaments, we show that actin microfilament remodeling is part of fenestra biogenesis in this model. Furthermore, by using a loss-of-function approach, we show that the diaphragm protein PV-1 is necessary for fenestral pore architecture and the ordered arrangement of fenestrae in sieve plates. Together, these data provide insight into the cell biology of fenestra formation and open up the future study of the fenestra to a combined morphological and biochemical analysis.