Hepatocyte γ-catenin compensates for conditionally deleted β-catenin at adherens junctions.
Hepatocyte γ-catenin compensates for conditionally deleted β-catenin at adherens junctions.
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DOI：
10.1016/j.jhep.2011.03.014
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发表时间：
2011-12
影响因子：
25.7
通讯作者：
Monga, Satdarshan P. S.
中科院分区：
文献类型：
--
作者：
Wickline, Emily Diane;Awuah, Prince Kwaku;Behari, Jaideep;Ross, Mark;Stolz, Donna B.;Monga, Satdarshan P. S.
Wnt/β-连环蛋白信号传导在肝脏生理学中是重要的。β-连环蛋白在粘附连接（AJ）中也是关键的。在这里，我们研究了肝细胞特异性β-连环蛋白条件无效小鼠（KO），AJ和相关紧密连接（TJ）的任何变化。利用基因组、PCR、Western blot、免疫组化、免疫荧光和共沉淀研究，我们比较和对比KO和同窝野生型（WT）对照肝脏中AJ和TJ的组成。我们证明了WT肝脏上皮细胞中的E-钙粘蛋白-β-连环蛋白相关性，其在科斯中丢失。虽然α-连环蛋白、E-钙粘蛋白和F-肌动蛋白的总水平适度降低，但KO肝脏显示γ-连环蛋白/斑珠蛋白增加。通过共沉淀，在WT肝脏中观察到E-钙粘蛋白-β-连环蛋白-F-肌动蛋白缔合，但在KO肝脏中E-钙粘蛋白-γ-连环蛋白-F-肌动蛋白缔合明显。在KO肝脏中，γ-连环蛋白在基线时定位于肝细胞膜。虽然γ-连环蛋白基因表达保持不变，但通过免疫沉淀在KO肝脏中观察到丝氨酸和苏氨酸磷酸化的γ-连环蛋白增加，但酪氨酸磷酸化的γ-连环蛋白没有增加。通过免疫荧光，在KO和WT中，在部分肝切除术后40和72小时的肝再生中观察到γ-连环蛋白在肝细胞膜上持续存在，而没有任何核定位。TJ的分析揭示了KO肝脏中封闭蛋白-2的缺乏和JAM-A和封闭蛋白-1水平的增加。在肝细胞中β-连环蛋白不存在的情况下，γ-连环蛋白足以维持AJ，但它缺乏核定位。此外，β-catenin-claudin-2可能是AJ和TJ之间串扰的重要机制。
Wnt/β-catenin signaling is important in liver physiology. β-Catenin is also pivotal in adherens junctions (AJ). Here, we investigate hepatocyte-specific β-catenin-conditional null mice (KO), for any alterations in AJ and related tight junctions (TJ). Using genearray, PCR, western blot, immunohistochemistry, immunofluorescence and coprecipitation studies, we compare and contrast the composition of AJ and TJ in KO and littermate wild-type (WT) control livers. We demonstrate E-cadherin-β-catenin association in epithelial cells in WT livers, which is lost in the KOs. While total levels of α-catenin, E-cadherin and F-actin were modestly decreased, KO livers show increased γ-catenin/plakoglobin. By co-precipitation, E-cadherin-β-catenin-F-actin association was observed in WT livers, but E-cadherin-γ-catenin-F-actin association was evident in KO livers. γ-Catenin was localized at the hepatocyte membrane at baseline in the KO liver. While γ-catenin gene expression remained unaltered, an increase in serine- and threonine-phosphorylated, but not tyrosine-phosphorylated γ-catenin was observed in KO livers by immunoprecipitation. A continued presence of γ-catenin at hepatocyte membrane without any nuclear localization was observed in liver regeneration after partial-hepatectomy at 40 and 72 hours in both KO and WT by immunofluorescence. Analysis of TJ revealed lack of claudin-2 and increased levels of JAM-A and claudin-1 in KO livers. γ-Catenin adequately maintains AJ in the absence of β-catenin in hepatocytes, however it lacks nuclear localization. Also, β-catenin-claudin-2 may be an important mechanism of crosstalk between the AJ and TJ.
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影响因子：
--
作者：
PASDAR, M;LI, Z;CHLUMECKY, V
通讯作者：
CHLUMECKY, V
DOI：
10.1006/bbrc.1999.1002
发表时间：
1999-08-02
影响因子：
3.1
作者：
Hiscox, S;Jiang, WG
通讯作者：
Jiang, WG
影响因子：
4.8
作者：
Konopka, Genevieve;Tekiela, Jackie;Duncan, Stephen A.
通讯作者：
Duncan, Stephen A.
影响因子：
7.8
作者：
Salomon, D;Sacco, PA;BenZeev, A
通讯作者：
BenZeev, A
DOI：
10.1073/pnas.92.23.10629
发表时间：
1995-11-07
影响因子：
11.1
作者：
NUSRAT, A;GIRY, M;MADARA, JL
通讯作者：
MADARA, JL