Caveolae, fenestrae and transendothelial channels retain PV1 on the surface of endothelial cells.
Caveolae, fenestrae and transendothelial channels retain PV1 on the surface of endothelial cells.
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DOI：
10.1371/journal.pone.0032655
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Stan RV
中科院分区：
文献类型：
--
作者：
Tkachenko E;Tse D;Sideleva O;Deharvengt SJ;Luciano MR;Xu Y;McGarry CL;Chidlow J;Pilch PF;Sessa WC;Toomre DK;Stan RV
PV 1蛋白是气孔和窗孔隔膜的重要组成部分，其形成于内皮细胞（EC）的质膜上，在结构如小窝、窗孔和跨内皮通道上。小鼠中PV 1的敲除导致子宫内和围产期死亡。为了能够解释复杂的PV 1敲除表型，关键是要确定隔膜的形成是否是PV 1的唯一细胞作用。我们通过测量完全和部分去除能够形成隔膜的结构对PV 1蛋白水平的影响来解决这个问题。通过敲除caveolin-1或cavin-1来去除小鼠中的caveolae导致肺中的PV 1蛋白水平显著降低，但不是肾脏。PV 1减少的幅度与这些器官的微血管中能够形成隔膜的结构的丰度相关。在肺EC的小窝的情况下，不影响PV 1的转录或翻译，但它引起了急剧增加的PV 1蛋白内化率通过网格蛋白和动力蛋白的非依赖性途径，随后在溶酶体中降解。因此，PV 1通过能够形成隔膜的结构保留在EC的细胞表面上，但在没有这些结构的情况下经历快速内化和降解，这表明隔膜的形成是PV 1的唯一作用。
PV1 protein is an essential component of stomatal and fenestral diaphragms, which are formed at the plasma membrane of endothelial cells (ECs), on structures such as caveolae, fenestrae and transendothelial channels. Knockout of PV1 in mice results in in utero and perinatal mortality. To be able to interpret the complex PV1 knockout phenotype, it is critical to determine whether the formation of diaphragms is the only cellular role of PV1. We addressed this question by measuring the effect of complete and partial removal of structures capable of forming diaphragms on PV1 protein level. Removal of caveolae in mice by knocking out caveolin-1 or cavin-1 resulted in a dramatic reduction of PV1 protein level in lungs but not kidneys. The magnitude of PV1 reduction correlated with the abundance of structures capable of forming diaphragms in the microvasculature of these organs. The absence of caveolae in the lung ECs did not affect the transcription or translation of PV1, but it caused a sharp increase in PV1 protein internalization rate via a clathrin- and dynamin-independent pathway followed by degradation in lysosomes. Thus, PV1 is retained on the cell surface of ECs by structures capable of forming diaphragms, but undergoes rapid internalization and degradation in the absence of these structures, suggesting that formation of diaphragms is the only role of PV1.
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影响因子：
10.8
作者：
Bates DO
通讯作者：
Bates DO
DOI：
10.1083/jcb.200903053
发表时间：
2009-06-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bastiani M;Liu L;Hill MM;Jedrychowski MP;Nixon SJ;Lo HP;Abankwa D;Luetterforst R;Fernandez-Rojo M;Breen MR;Gygi SP;Vinten J;Walser PJ;North KN;Hancock JF;Pilch PF;Parton RG
通讯作者：
Parton RG
影响因子：
11.8
作者：
Macia, Eric;Ehrlich, Marcelo;Kirchhausen, Tomas
通讯作者：
Kirchhausen, Tomas
影响因子：
7.8
作者：
Goss, John W.;Toomre, Derek K.
通讯作者：
Toomre, Derek K.
影响因子：
56.9
作者：
Drab, M;Verkade, P;Kurzchalia, TV
通讯作者：
Kurzchalia, TV