Regulation of fenestra formation via actin-dynamin2 interaction in rat pituitary endothelial cells.
Regulation of fenestra formation via actin-dynamin2 interaction in rat pituitary endothelial cells.
复制标题
通过大鼠垂体内皮细胞中肌动蛋白-dynamin2 相互作用调节窗孔形成。
DOI：
10.1007/s00441-022-03685-y
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Suzuki T
中科院分区：
文献类型：
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作者：
Nakakura T;Tanaka H;Suzuki T
内皮窗是由质膜囊泡相关蛋白（PLVAP）组成的隔膜分隔的跨细胞孔。它们作为肽激素和其他物质的通道。质膜的内陷是窗孔形成所必需的。肌动蛋白细胞骨架对于内吞囊泡从内陷的质膜上脱落是必不可少的。因此，我们研究了参与的肌动蛋白细胞骨架在窗孔形成培养的内皮细胞分离的前叶（AL）的大鼠垂体，使用免疫荧光和扫描电子显微镜。抑制聚合和解聚的肌动蛋白细胞骨架的latrunculin A和jasplakineline，分别显着增加PLVAP阳性筛板面积和数量的窗孔。茉莉内酯显着影响细胞表面窗孔的排列，导致窗孔出现平行的蛇形沟。这些结果表明，肌动蛋白细胞骨架不仅诱导窗孔的形成，而且还调节细胞排列。发动蛋白是内陷质膜的一种断裂蛋白，与肌动蛋白细胞骨架相互作用。我们发现，dynamin 2主要表达在大鼠AL的内皮细胞。然后，我们研究dyngo-4a，dynamin 1和dynamin 2的有效抑制剂，对窗孔形成的处理dynamin 2的功能。结果，PLVAP阳性面积通过处理显著增加。这些结果表明，肌动蛋白-dynamin 2相互作用是必不可少的大鼠AL的内皮细胞的窗孔形成的控制。总之，肌动蛋白细胞骨架和dynamin 2作为调节器的内皮窗孔形成的功能。
Endothelial fenestrae are transcellular pores divided by a diaphragm consisting of plasmalemma vesicle-associated protein (PLVAP). They function as a channel for peptide hormones and other substances. Invagination of the plasma membrane is necessary for the fenestra formation. The actin cytoskeleton is essential for scission of endocytic vesicles from the invaginated plasma membrane. Therefore, we examined the involvement of the actin cytoskeleton in fenestra formation in cultured endothelial cells isolated from the anterior lobe (AL) of the rat pituitary, using immunofluorescence and scanning electron microscopy. Inhibition of polymerization and depolymerization of the actin cytoskeleton by latrunculin A and jasplakinolide, respectively, remarkably increased the PLVAP-positive sieve plate area and number of fenestrae. Jasplakinolide significantly affected the arrangement of the fenestra on the cell surface, resulting in parallel serpentine furrows of the fenestra. These results suggest that the actin cytoskeleton not only induces fenestra formation but also regulates cell arrangement. Dynamin is a scission protein of the invaginated plasma membrane and interacts with the actin cytoskeleton. We found that dynamin2 is mainly expressed in the endothelial cells of the rat AL. We then investigated the function of dynamin2 by the treatment with dyngo-4a, a potent inhibitor of dynamin1 and dynamin2, on the fenestra formation. As a result, the PLVAP-positive area is significantly increased by the treatment. These results show that the actin-dynamin2 interaction is essential for the control of the fenestra formation in endothelial cells of rat AL. In conclusion, the actin cytoskeleton and dynamin2 function as regulators of endothelial fenestra formation.