In vivo, villin is required for Ca(2+)-dependent F-actin disruption in intestinal brush borders.
In vivo, villin is required for Ca(2+)-dependent F-actin disruption in intestinal brush borders.
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DOI：
10.1083/jcb.146.4.819
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发表时间：
1999-08-23
期刊：
影响因子：
--
通讯作者：
Robine S
中科院分区：
文献类型：
--
作者：
Ferrary E;Cohen-Tannoudji M;Pehau-Arnaudet G;Lapillonne A;Athman R;Ruiz T;Boulouha L;El Marjou F;Doye A;Fontaine JJ;Antony C;Babinet C;Louvard D;Jaisser F;Robine S
绒毛蛋白是一种肌动蛋白结合蛋白，定位于肠道和肾脏刷状缘。在体外，绒毛蛋白已被证明以Ca 2+依赖的方式捆绑和切断F-肌动蛋白。我们产生基因敲除小鼠来研究绒毛蛋白在体内的作用。在villin-null小鼠，没有观察到显着的变化，在微绒毛的超微结构或在定位和表达的肌动蛋白结合和膜蛋白的肠。有趣的是，突变小鼠和正常小鼠对细胞内Ca 2+升高的反应显著不同。在野生型动物中，孤立的刷状缘被破坏的Ca 2+，而Ca 2+在绒毛空菌株没有影响。此外，增加细胞内Ca 2+的丝氨酸氨甲酰胆碱或粘膜Ca 2+离子载体A23187的应用废除了F-肌动蛋白标记，只有在野生型动物的刷状缘。这种F-肌动蛋白破坏也观察到在生理禁食/再喂养实验。经口给予葡聚糖硫酸钠（一种导致结肠上皮损伤的药物）可诱导大的粘膜病变，导致缺乏绒毛蛋白的小鼠在第13天的死亡概率（36 ± 9.6%）高于野生型小鼠（70 ± 8.8%）。这些结果表明，在体内，绒毛是不必要的F-肌动蛋白微丝的集束，但它是必要的各种信号引起的重组。我们推测，这种性质可能涉及与细胞损伤有关的细胞可塑性。
Villin is an actin-binding protein localized in intestinal and kidney brush borders. In vitro, villin has been demonstrated to bundle and sever F-actin in a Ca2+-dependent manner. We generated knockout mice to study the role of villin in vivo. In villin-null mice, no noticeable changes were observed in the ultrastructure of the microvilli or in the localization and expression of the actin-binding and membrane proteins of the intestine. Interestingly, the response to elevated intracellular Ca2+ differed significantly between mutant and normal mice. In wild-type animals, isolated brush borders were disrupted by the addition of Ca2+, whereas Ca2+ had no effect in villin-null isolates. Moreover, increase in intracellular Ca2+ by serosal carbachol or mucosal Ca2+ ionophore A23187 application abolished the F-actin labeling only in the brush border of wild-type animals. This F-actin disruption was also observed in physiological fasting/refeeding experiments. Oral administration of dextran sulfate sodium, an agent that causes colonic epithelial injury, induced large mucosal lesions resulting in a higher death probability in mice lacking villin, 36 ± 9.6%, compared with wild-type mice, 70 ± 8.8%, at day 13. These results suggest that in vivo, villin is not necessary for the bundling of F-actin microfilaments, whereas it is necessary for the reorganization elicited by various signals. We postulate that this property might be involved in cellular plasticity related to cell injury.
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影响因子：
7.8
作者：
Bartles, J R;Zheng, L;Li, A;Wierda, A;Chen, B
通讯作者：
Chen, B
影响因子：
7.8
作者：
BADER, MF;TRIFARO, JM;AUNIS, D
通讯作者：
AUNIS, D
影响因子：
2.5
作者：
CHAFEL, MM;SHEN, WY;MATSUDAIRA, P
通讯作者：
MATSUDAIRA, P
DOI：
10.1083/jcb.108.2.495
发表时间：
1989-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Coluccio LM;Bretscher A
通讯作者：
Bretscher A
DOI：
10.1073/pnas.85.14.4986
发表时间：
1988-07-01
影响因子：
11.1
作者：
BAZARI, WL;MATSUDAIRA, P;AHMED, Y
通讯作者：
AHMED, Y